Substituted arylalkanoic acid derivatives and use thereof

ABSTRACT

A compound represented by the formula (I): 
     
       
         
         
             
             
         
       
     
     [In the formula, Link represents a saturated or unsaturated straight hydrocarbon chain having 1 to 3 carbon atoms, C 2  to C 6  in the aromatic ring (E) independently represent a ring-constituting carbon atom, one of the ring-constituting carbon atoms may be replaced with V, V represents nitrogen atom, or carbon atom substituted with Zx, Zx represents a saturated alkyl group having 1 to 4 carbon atoms and the like, Rs represents -D-Rx etc., D represents a single bond, oxygen atom and the like, Rx represents a saturated alkyl group having 3 to 8 carbon atoms and the like, AR represents a partially unsaturated or completely unsaturated condensed bicyclic carbon ring or a heterocyclic ring, and Y represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms and the like] or a salt thereof. A compound having prostaglandin production-suppressing action and leukotriene production-suppressing action is provided.

This application is a Divisional of co-pending application Ser. No.10/568,185 filed on Feb. 13, 2006 and for which priority is claimedunder 35 U.S.C. §120. Application Ser. No. 10/568,185 is the nationalphase of PCT International Application No. PCT/JP2004/011953 filed onAug. 13, 2004 under 35 U.S.C. §371. This application also claimspriority to U.S. Provisional Application No. 60/495,734, filed Aug. 18,2003 under 35 U.S.C. §119(e) and JP2003-293590, filed in Japan on Aug.14, 2003 under 35 U.S.C. §119(a). The entire contents of each of theabove-identified applications are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to a novel substituted arylalkanoic acidderivative. More specifically, the present invention relates to asubstituted arylalkanoic acid derivative having an action as amedicament and a synthetic intermediate of said compound.

BACKGROUND ART

Various kinds of prostaglandins and various kinds of leukotrienes areproduced in the bodies of mammals in response to variety of stimuli suchas inflammatory stimuli and physical stimuli.

Both of prostaglandins and leukotrienes are metabolites of arachidonicacid, and they are physiologically active substances referred to aslipid mediators, and they cause various physiological responses ofmammals by binding to receptors expressed on surfaces of various cellsor in the cells.

Arachidonic acid is produced from a phospholipid as a substrate, such asphosphatidylcholine which is a cell membrane component, with the aid ofan enzymatic activity of phospholipase A₂ (PLA₂).

Arachidonic acid produced by the action of PLA₂ is converted intoprostaglandin (PG) H₂ with the aid of an enzymatic activity ofconstitutive type cyclooxygenase (COX) 1 or inducible type COX-2, andfurther converted into PGE₂, PGD₂, PGF₂ α, PGI₂, thromboxane (TX) A₂ andthe like with the aid of each synthetic enzyme. Further, arachidonicacid is also metabolized by the action of 5-lipoxygenase (5-LO) andthereby converted to leukotriene (LT) A₄, and further converted to LTB₄,LTC₄, LTD₄, LTE₄ and the like by the enzymatic activities of LTA₄hydrolase, LTC₄ synthase, glutathione S-transferase and the like[Goodman & Gilman, Pharmacological Basis of Therapeutics, 9th edition,p. 801, 1999 (Hirokawa Shoten); Funk, C. D., SCIENCE, vol. 294, p. 1871,2001].

Prostaglandins bind to each specific receptor to cause inflammatoryreactions such as fervescence, enhancement of vascular permeability,vasodilation, swelling and pain, bronchial smooth muscle contraction,platelet aggregation, tumor cell proliferation, enhancement of boneresorption, nerve cell degeneration and the like, and thus playimportant roles in expression of symptoms or pathological formation forvarious diseases.

Leukotrienes are physiologically active substances which bind to eachspecific receptor to cause inflammatory reactions such as excessiveaccumulation of leucocytes and enhancement of vascular permeability,smooth muscle contraction, mucus secretion, proliferation of tumor cellsand the like, and thus play important roles in expression of symptoms orpathological formation for various diseases.

Although inflammatory reactions themselves are essential reactions forliving bodies to survive when they face pathogenic substances andaffections, they are sometimes excessively caused or continue withoutany reason for providing evident benefit under certain situations or incertain diseases [Goodman & Gilman, Pharmacological Basis ofTherapeutics, 9th edition, p. 827, 1999 (Hirokawa Shoten)]. Thecondition of living body referred to in this specification wherein anacute or chronic inflammatory reaction is observed means a conditionthat an excessive or unbeneficial acute or temporary inflammatoryreaction or chronic and persistent inflammatory reaction is caused.Further, an inflammatory reaction refers to a series of events caused bystimuli, for example, physical hazards such as heat, infectivesubstances, ischemia, antigen/antibody reaction and the like, and it isaccompanied by flare, swelling, hyperalgesia, algesic onset and the likeas well-known macroscopic clinical symptoms. It is known that, ashistological mechanisms for these reactions, vasodilation, enhancementof vascular permeability, infiltration of leucocytes and phagocytes,histological decomposition and fibrosing and the like are caused[Goodman & Gilman, Pharmacological Basis of Therapeutics, 9th edition,p. 827, 1999 (Hirokawa Shoten)]. It is known that many of thesehistological reactions are caused by prostaglandins and/or leukotrienes,and prostaglandins and/or leukotrienes plays important roles ininflammatory reactions.

For example, it was reported that, in a pathological tissue ofrheumatoid arthritis, which is an autoimmune and chronic inflammatorydisease, expression of COX-2 and production of PGE₂ and TXA₂ as well asexpression of 5-LO and production of LTB₄ were observed (Bonnet et al.,Prostaglandins, 1995, vol. 50, p. 127), and in a mouse deficient inFLAP, which is a protein required for activation of 5-LO, symptom ofcollagen-induced arthritis, which is a pathological model of chronicrheumatoid arthritis, was milder compared with that in a wild-type mouse(Griffiths et al., J. Exp. Med., 1997, vol. 185, p. 1123), and thus ithas been suggested that prostaglandins and leukotrienes play importantroles in the pathological formation of chronic rheumatoid arthritis.

It was reported that, in a pathological tissue of bronchial asthma, oneof chronic allergic diseases, excessive production of PGD₂ and TXA₂ aswell as excessive production of LTC₄ and LTD₄ were observed (Wenzel etal., Am Rev. Respir. Dis., 1990, vol. 142, p. 112), and an airwayhypersensitive reaction, which is a pathological model of bronchialasthma, was unlikely to occur in a PGD₂ receptor-deficient mouse(Matsuoka et al., SCIENCE, vol. 287, p. 2013, 2000). Thus, it has beendemonstrated that roles of prostaglandins and leukotrienes are importantin bronchial asthma.

In a cerebral tissue after ischemic reperfusion, expression of COX-2increased, and concentrations of PGE₂ and TXA₂ increased, whereasactivity of 5-LO increased, and production amount of LTC₄ increased(Ohtsuki et al., Am. J. Physiol., 1995, vol. 268, p. 1249). Thus, it isknown that prostaglandins and leukotrienes play important roles information of infarct that is accepted as an ischemic reperfusion injury.

It has been revealed that, in a pathological tissue of Alzheimer'sdisease, one of the diseases with neurodegeneration, the COX activityand 5-LO activity increased, prostaglandins and leukotrienes causeformation of the β-amyloid protein, one of the pathogenic substances ofAlzheimer's disease, and further cause degeneration of nerve cells(Sugaya et al., Jpn. J. Pharmacol., 2000, vol. 82, p. 85), and thus itis believed that prostaglandins and leukotrienes play important roles inthe formation of neurodegenerative diseases such as Alzheimer's disease.

Furthermore, for example, it was reported that, in a pathological tissueof colon cancer, COX and 5-LO were expressed, and amounts of productionof prostaglandins and leukotrienes were increased (Dreyling et al.,Biochim. Biophys. Acta., 1986, vol. 878, p. 184), and leukotriene causedincrease in colon cancer cells (Qiao et al., Biochim. Biophys. Acta,1995, vol. 1258, p. 215; Hong et al., Cancer Res., 1999, vol. 59, p.2223). Thus, it is believed that prostaglandins and leukotrienes playimportant roles also in tissues of large bowel cancer.

Involvement of prostaglandins and/or leukotrienes in diseases andpathological conditions is not limited to those diseases exemplifiedabove, and it has been demonstrated that prostaglandins and/orleukotrienes are involved in variety of conditions, various diseases, orvarious pathological conditions where acute or chronic inflammatoryreactions are observed and their roles are important.

For the above reason, various prostaglandin production suppressors orleukotriene production suppressors are used as agents for prophylacticor therapeutic treatment of conditions, various diseases or pathologicalconditions where an acute or chronic inflammatory reaction isrecognized. Various non-steroidal anti-inflammatory drugs (NSAIDS) asmedicaments having a prostaglandin production-suppressing action areavailable and used as therapeutic agents for chronic rheumatoidarthritis and osteoarthritis, antiphlogistic-analgesic agents for injuryand the like, prophylactic agents for cerebral infarction or myocardialinfarction, prophylactic agents for colon polyposis and the like.However, the class of NSAIDS suppress only production of prostaglandins,and as a result, they increase amounts of production of leukotrienes,and exhibit side effects such as asthmatic attack and gastrointestinalinjury as well as renal disturbance. Furthermore, a difference betweenan effective dose and a dose inducing the side effects is small in theseNSAIDS, and no satisfactory agent is available from a viewpoint oftherapeutic effect. A 5-LO inhibitor is available which is described inEuropean Patent No. 279263 as a medicament having a leukotrieneproduction-suppressing action, and the inhibitor is known as aprophylactic agent for asthma. However, since the agent causes sideeffects such as hepatic disorder, its dosage is limited, and the agentis not satisfactory also from a viewpoint of therapeutic effect. Sincesteroid agents suppress production of both of prostaglandins andleukotrienes, they are used as prophylactic agents or therapeutic agentsfor conditions of living bodies, various diseases and pathologicalconditions where various acute or chronic inflammatory reactions areobserved. However, their actions are not limited to the lipid mediatorproduction-suppressing action, and they exhibit severe side effects suchas induction and exacerbation of infectious diseases due to theimmunosuppression action, growth retardation due to normal cellantiproliferative activity, anetoderma and peptic ulcer. Therefore,their uses are limited.

Furthermore, for the above reasons, it is considered that compounds,that suppress the production of both of prostaglandins and leukotrienesand have reduced side effect, are effective as therapeutic agents orprophylactic agents for such conditions of living bodies, diseases orpathological conditions in mammals as described above, and methods ofusing such compounds together with medicaments available at present aremore effective therapeutic or prophylactic methods. Therefore,development of compounds suppressing the production of both ofprostaglandins and leukotrienes, and manufacture of pharmaceuticalpreparations thereof are strongly desired.

As compounds structurally similar to the compounds of the presentinvention, for example, biphenyl-5-alkanoic acid derivatives and usethereof are described in WO99/19291. However, the moiety of thesecompounds that corresponds to “AR” included in the formula (I) of thecompounds of the present invention is phenyl group, and thus structuralfeatures of the above compounds are different. Further, biarylphospholipase A² inhibitors are described in U.S. Pat. No. 5,391,817[Japanese Patent Unexamined Publication (Kokai) No. 7-22399]. However,the moiety of these compounds that corresponds to “AR” included in theformula (I) of the compounds of the present invention is only defined tobe phenyl group, and thus the structural features of the above compoundsare different. Bicyclic heterocyclic compounds are described inWO00/35886 as protease inhibitors. However, the substituents of thesecompounds on the moiety that corresponds to “AR” included in the formula(I) of the compounds of the present invention are different, andfurther, the publication is completely silent about whether or not thecompounds described in the above patent document have any prostaglandinproduction-suppressing action or leukotriene production-suppressingaction.

[Patent document 1] WO99/19291[Patent document 2] U.S. Pat. No. 5,391,817[Patent document 3] WO00/35886

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide a novel compound havingsuperior prostaglandin production-suppressing action and leukotrieneproduction-suppressing action. Another object of the present inventionis to provide a compound for prophylactic and/or therapeutic treatmentof various inflammatory diseases, autoimmune diseases, allergicdiseases, pain and fibrosis in mammals caused by lipid mediators. Afurther object of the present invention is to provide a pharmaceuticalcomposition containing such a compound. A still further object of thepresent invention is to provide an intermediate for the production ofthe compound. These objects and other objects as well as advantages ofthe present invention will be apparent for those skilled in the art fromthe following descriptions.

In order to achieve the aforementioned objects, the inventors of thepresent invention conducted various researches. As a result, they foundthat the substituted arylalkanoic acid derivatives represented by thefollowing general formula, which are novel compounds, had superiorprostaglandin production-suppressing action and leukotrieneproduction-suppressing action, and thus accomplished the presentinvention.

The present invention is embodied by, for example, those described inthe following (1) to (191).

(1) A compound represented by the formula (I):

[In the formula, Link represents a saturated or unsaturated straighthydrocarbon chain having 1 to 3 carbon atoms.

C², C³, C⁴, C⁵, and C⁶ in the aromatic ring (E) independently representa ring-constituting carbon atom. One of the ring-constituting carbonatoms to which Rs and AR do not bind may be replaced with V.

V represents nitrogen atom, or carbon atom substituted with Zx. Zxrepresents a linear or branched saturated alkyl group having 1 to 4carbon atoms, fluorine atom, chlorine atom, bromine atom, nitro group,—OR⁹, or —N(Rn¹)(Rn²). R⁹ represents hydrogen atom, a lower alkyl grouphaving 1 to 4 carbon atoms, or -A⁶-Qp, wherein A⁶ represents a singlebond or methylene, Qp represents phenyl group, and the phenyl group maybe substituted with one of T¹ or two or more of the same or differentT¹. T¹ represents a linear or branched saturated alkyl group having 1 to4 carbon atoms, hydroxyl group, fluorine atom, chlorine atom, bromineatom, trifluoromethyl group, nitro group, an alkoxy group having 1 to 4carbon atoms, or a mono- or dialkylamino group having 1 to 4 carbonatoms. Rn¹ represents hydrogen atom or a linear or branched saturatedalkyl group having 1 to 4 carbon atoms, Rn² has the same meaning as Rn¹,or represents —COR²³ or —SO₂R²⁴, or binds to Rn¹ to form a 3- to6-membered ring together with the nitrogen atom to which they bind toform a saturated nitrogen-containing cycloalkyl group or morpholinogroup. R²³ represents hydrogen atom, a lower alkyl group having 1 to 4carbon atoms, a lower alkoxy group having 1 to 4 carbon atoms, —O-A⁶-Qp,or —N(R²⁵)(R²⁶). R²⁵ represents hydrogen atom, or a linear or branchedsaturated alkyl group having 1 to 4 carbon atoms. R²⁶ has the samemeaning as R²⁵, or binds to R²⁵ to form a 3- to 6-membered ring togetherwith the nitrogen atom to which they bind to form a saturatednitrogen-containing cycloalkyl group or morpholino group. R²⁴ representsa lower alkyl group having 1 to 4 carbon atoms, amino group, or a mono-or dialkylamino group having 1 to 4 carbon atoms.

Rs represents -D-Rx or —N(Ry)(Rz).

D represents a single bond, oxygen atom, sulfur atom, —S(O)—, —S(O)₂—,or —C(O).

Rx represents a linear or branched saturated alkyl group having 3 to 8carbon atoms, or represents Ra represented by the following formula:

R¹(CH₂)_(k)—  (Ra)

Rb represented by the following formula:

or Rc represented by the following formula:

k in Ra represents 0 or an integer of 1 to 3. R¹ represents a saturatedcyclic alkyl group having 3 to 7 carbon atoms, or a condensed saturatedcyclic alkyl group having 6 to 8 carbon atoms, and R¹ may be substitutedwith one of lower alkyl group having 1 to 4 carbon atoms or two or moreof the same or different lower alkyl groups having 1 to 4 carbon atoms.Q in Rb represents a partially unsaturated or completely unsaturatedmonocyclic or condensed bicyclic carbon ring or a heterocyclic ring (q),and binds to A² at an arbitrary position. The heterocyclic ring (q)contains the same or different 1 to 4 ring-constituting heteroatomsselected from the group consisting of nitrogen atom, oxygen atom, andsulfur atom. A¹ represents a single bond or an alkylene (a) having 1 to3 carbon atoms, and the alkylene (a) may be substituted with a loweralkyl group having 1 to 4 carbon atoms or phenyl group. A² represents asingle bond, oxygen atom, sulfur atom, —S(O)—, —S(O)₂—, or —N(R⁴)—(provided that when A² represents oxygen atom, sulfur atom, —S(O)—,—S(O)₂— or —N(R⁴)—, A¹ represents ethylene or trimethylene). R² and R³independently represent hydrogen atom, a linear or branched saturatedalkyl group having 1 to 4 carbon atoms, oxo group, thioxo group,fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, —OR⁵,—N(R⁶)(R⁶′), —NHCOR⁷, —NHSO₂R⁸, or -A⁶-Qa, or they bind to each other torepresent methylenedioxy group. Qa represents a partially unsaturated orcompletely unsaturated monocyclic or condensed bicyclic carbon ring or aheterocyclic ring (qa), binds to A⁶ at an arbitrary position on thering, and may be substituted with one of T¹ or two or more of the sameor different T¹. The heterocyclic ring (qa) contains the same ordifferent 1 to 4 ring-constituting heteroatoms selected from the groupconsisting of nitrogen atom, oxygen atom, and sulfur atom. R⁴ and R⁶independently represent hydrogen atom or a lower alkyl group having 1 to4 carbon atoms. R⁵ and R⁷ independently represent hydrogen atom, a loweralkyl group having 1 to 4 carbon atoms, or -A⁶-Qa. R⁸ represents a loweralkyl group having 1 to 4 carbon atoms. R⁶′ has the same meaning as R⁶,or binds to R⁶ to form a 3- to 6-membered ring together with thenitrogen atom to which they bind to represent a saturatednitrogen-containing cycloalkyl group or morpholino group. p in Rcrepresents an integer of 2 to 4. A⁴ represents a single bond, methylene,or ethylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa. Rerepresents an alkyl group having 1 to 8 carbon atoms, -A⁶-Qa,—(CH₂)_(i)R¹⁴, —OR²⁸, —SR²⁸, or —N(R²⁹)(R³⁰). i represents an integer of1 to 3, R¹⁴ represents hydroxyl group, an alkoxy group having 1 to 4carbon atoms, carboxyl group, or an N,N-dialkylcarbamoyl group having 1to 4 carbon atoms. R²⁸ represents an alkyl group having 1 to 8 carbonatoms, or -A⁶-Qa. R²⁹ represents an alkyl group having 1 to 8 carbonatoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, or -A⁶-Qa.R³⁰ represents hydrogen atom or a lower alkyl group having 1 to 4 carbonatoms, or binds to R²⁹ to form a 3- to 6-membered ring together with thenitrogen atom to which they bind to represent a saturatednitrogen-containing cycloalkyl group or morpholino group.

Rz has the same meaning as Rx, or Rz represents methyl group, ethylgroup, or -A⁵-Re. Ry represents hydrogen atom, an alkyl group having 1to 8 carbon atoms, or -A⁶-Qp, or Ry may bind to Rz to form, togetherwith a nitrogen atom to which they bind, a saturated or unsaturated 3 to7-membered nitrogen-containing cyclic group, wherein saidnitrogen-containing cyclic group may optionally be substituted with oneor two lower alkyl groups having 1 to 4 carbon atoms wherein said twoalkyl groups may be the same or different.

AR represents a partially unsaturated or completely unsaturatedcondensed bicyclic carbon ring or a heterocyclic ring (ar), and may besubstituted with one of Xa or two or more of the same or different Xa.The heterocyclic ring (ar) contains the same or different 1 to 4ring-constituting heteroatoms selected from the group consisting ofnitrogen atom, oxygen atom, and sulfur atom. Xa represents a linear orbranched saturated alkyl group having 1 to 4 carbon atoms, a saturatedcyclic alkyl group having 3 to 7 carbon atoms, oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, —(CH₂)_(i)R¹⁴,—OR¹⁰, —N(R¹¹)(R¹²), —SO₂R¹³, or —COR²⁷. R¹⁰ represents hydrogen atom, alower alkyl group having 1 to 4 carbon atoms, or —(CH₂)_(i)R¹⁴. R¹¹represents hydrogen atom or a lower alkyl group having 1 to 4 carbonatoms. R¹² represents hydrogen atom, a lower alkyl group having 1 to 4carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms, —COR¹⁵,or —SO₂R¹⁶, or binds to R¹¹ to form a 3- to 6-membered ring togetherwith the nitrogen atom to which they bind to represent a saturatednitrogen-containing cycloalkyl group or morpholino group. R¹⁵ representsa lower alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl grouphaving 2 to 4 carbon atoms, amino group, a mono- or dialkylamino grouphaving 1 to 4 carbon atoms, or -A⁶-Qa. R¹³ and R¹⁶ independentlyrepresent a lower alkyl group having 1 to 4 carbon atoms, amino group,or a mono- or dialkylamino group having 1 to 4 carbon atoms. R²⁷represents hydrogen atom, hydroxyl group, an alkoxy group having 1 to 4carbon atoms, a lower alkyl group having 1 to 4 carbon atoms, aminogroup, or a mono- or dialkylamino group having 1 to 4 carbon atoms.

Y represents hydrogen atom, a lower alkyl group having 1 to 4 carbonatoms, —(CH₂)_(m)N(R¹⁸)(R¹⁹), or C(R²⁰)₂OC(O)A³R²¹. Symbol m representsan integer of 2 or 3. R¹⁸ is the same as R¹⁹, or binds to R¹⁹ to form a3- to 6-membered ring together with the nitrogen atom to which they bindto represent a saturated nitrogen-containing cycloalkyl group ormorpholino group. R¹⁹ represents methyl group, ethyl group, or propylgroup. R²⁰ represents hydrogen atom, methyl group, ethyl group, orpropyl group. R²¹ represents a lower alkyl group having 1 to 4 carbonatoms, a cyclic saturated alkyl group having 3 to 6 carbon atoms, orphenyl group, and A³ represents a single bond, or oxygen atom. Thiscompound may sometimes be hereinafter referred to simply as “Compound(I)” of the present invention.”] or a salt thereof.

(1-2) The compound or salt thereof according to (1), wherein, in theformula (I), Link is —(CH₂)_(n)—, n is an integer of 1 to 3, Rz has thesame meaning as that of Rx or represents -A⁵-Re when Rs is —N(Ry)(Rz),and Ry is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, orA⁶-Qp, or Ry binds to Rz to form, together with a nitrogen atom to whichthey bind, a saturated or unsaturated 3 to 7-memberednitrogen-containing cyclic group.(2) The compound or salt thereof according to (1) or (1-2) mentionedabove, wherein, in the formula (I), AR binds to any atom among C² and C³in the aromatic ring (E).(3) The compound or salt thereof according to any one of (1) to (2)mentioned above, wherein, in the formula (I), n is an integer of 2 (thedescription of “according to any one of (1) to (2)” includes (1-2)mentioned above, and the same or similar description should be construedin the same manner hereinafter in the specification).(4) The compound or salt thereof according to any one of (1) to (3)mentioned above, wherein, in the formula (I), AR is a residue ofnaphthalene, benzofuran, benzo[b]thiophene, indole, benzothiazole,dihydro-3H-benzothiazole, quinoline, dihydro-1H-quinoline,benzo[d]isothiazole, 1H-indazole, benzo[c]isothiazole, 2H-indazole,imidazo[1,2-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, isoquinoline,dihydro-2H-isoquinoline, cinnoline, quinazoline, quinoxaline,1H-benzimidazole, benzoxazole, 1H-pyrrolo[3,2-b]pyridine,benzo[1,2,5]thiadiazole, 1H-benzotriazole,1,3-dihydropyrrolo[2,3-b]pyridine, 1,3-dihydrobenzimidazole,dihydro-3H-benzoxazole, phthalazine, [1,8]naphthalidine,[1,5]naphthalidine, 1H-pyrrolo[3,2-c]pyridine,1H-pyrrolo[2,3-c]pyridine, 1H-pyrazolo[4,3-b]pyridine,1H-pyrazolo[4,3-c]pyridine, 1H-pyrazolo[3,4-c]pyridine,1H-pyrazolo[3,4-b]pyridine, [1,2,4]triazolo[4,3-a]pyridine,thieno[3,2-c]pyridine, thieno[3,2-b]pyridine, 1H-thieno[3,2-c]pyrazole,benzo[d]isoxazole, benzo[c]isoxazole, indolizine, 1,3-dihydroindole,1H-pyrazolo[3,4-d]thiazole, 2H-isoindole,[1,2,4]triazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyrazine,1H-imidazo[4,5-b]pyrazine, 7H-purine, or 4H-chromene (the aforementionedresidue may be substituted with one of Xa or two or more of the same ordifferent Xa).(5) The compound or salt thereof according to any one of (1) to (3)mentioned above, wherein, in the formula (I), AR is naphthalen-2-ylgroup, naphthalen-1-yl group, benzofuran-5-yl group, benzofuran-4-ylgroup, benzofuran-2-yl group, benzo[b]thiophen-5-yl group,benzo[b]thiophen-4-yl group, benzo[b]thiophen-2-yl group, indol-5-ylgroup, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group,benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-ylgroup, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-ylgroup, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-ylgroup, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa).(6) The compound or salt thereof according to any one of (1) to (3)mentioned above, wherein, in the formula (I), AR is a residue ofnaphthalene, benzofuran, benzo[b]thiophene, indole, benzothiazole,dihydro-3H-benzothiazole, quinoline, dihydro-1H-quinoline,benzo[d]isothiazole, 1H-indazole, benzo[c]isothiazole, 2H-indazole,imidazo[1,2-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, isoquinoline, ordihydro-2H-isoquinoline (the aforementioned residue may be substitutedwith one of Xa or two or more of the same or different Xa).(7) The compound or salt thereof according to any one of (1) to (3)mentioned above, wherein, in the formula (I), AR is a residue ofcinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole,1H-pyrrolo[3,2-b]pyridine, benzo[1,2,5]thiadiazole, 1H-benzotriazole,1,3-dihydropyrrolo[2,3-b]pyridine, 1,3-dihydrobenzimidazole,dihydro-3H-benzoxazole, phthalazine, [1,8]naphthalidine,[1,5]naphthalidine, 1H-pyrrolo[3,2-c]pyridine,1H-pyrrolo[2,3-c]pyridine, 1H-pyrazolo[4,3-b]pyridine,1H-pyrazolo[4,3-c]pyridine, 1H-pyrazolo[3,4-c]pyridine,1H-pyrazolo[3,4-b]pyridine, [1,2,4]triazolo[4,3-a]pyridine,thieno[3,2-c]pyridine, thieno[3,2-b]pyridine, 1H-thieno[3,2-c]pyrazole,benzo[d]isoxazole, benzo[c]isoxazole, indolizine, 1,3-dihydroindole,1H-pyrazolo[3,4-d]thiazole, 1H-pyrazolo[3,4-d]thiazole, 2H-isoindole,[1,2,4]triazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyrazine,1H-imidazo[4,5-b]pyrazine, 7H-purine, or 4H-chromene (the aforementionedresidue may have one of Xa or two or more of the same or different Xa).(8) The compound or salt thereof according to any one of (1) to (7)mentioned above, wherein, in the formula (I), Rs is -D-Rx or —N(Ry)(Rz),D is a single bond, oxygen atom, sulfur atom, —S(O)—, —S(O)₂—, or—C(O)—, Rx is a linear or branched saturated alkyl group having 3 to 8carbon atoms, or Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, R¹is a saturated cyclic alkyl group having 3 to 7 carbon atoms or acondensed saturated cyclic alkyl group having 6 to 8 carbon atoms, R¹may be substituted with one of lower alkyl group having 1 to 4 carbonatoms or two or more of the same or different lower alkyl groups having1 to 4 carbon atoms, Q in Rb is phenyl group, thienyl group, furylgroup, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group,thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group,oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolylgroup, naphthyl group, tetrahydronaphthyl group, indanyl group, indenylgroup, quinolyl group, isoquinolyl group, indolyl group, benzofurylgroup, benzothienyl group, benzimidazolyl group, benzoxazolyl group,benzothiazolyl group, indazolyl group, 4H-chromenyl group,dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group,pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group,thienopyrazolyl group, 1,3-dihydrobenzimidazole group,dihydro-3H-benzoxazole group, or dihydro-3H-benzothiazole group (theaforementioned groups binds to A² at an arbitrary position), A¹ is asingle bond or an alkylene (a) having 1 to 3 carbon atoms, the alkylene(a) may be substituted with a lower alkyl group having 1 to 4 carbonatoms or phenyl group, A² is a single bond, oxygen atom, sulfur atom,—S(O)—, —S(O)₂—, or —N(R⁴)— (provided that when A² represents oxygenatom, sulfur atom, —S(O)—, —S(O)₂—, or —N(R⁴)—, A¹ represents ethyleneor trimethylene), R² and R³ independently represent hydrogen atom, alinear or branched saturated alkyl group having 1 to 4 carbon atoms, oxogroup, thioxo group, fluorine atom, chlorine atom, bromine atom,trifluoromethyl group, —OR⁶, —N(R⁶)(R⁶′), —NHCOR⁷, —NHSO₂R⁸, or -A⁶-Qa,or they bind to each other to represent methylenedioxy group, Qa isphenyl group, pyridyl group, oxazolyl group, isoxazolyl group, thiazolylgroup, isothiazolyl group, imidazolyl group, pyrazolyl group,oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolylgroup, naphthyl group, indanyl group, indenyl group, quinolyl group,isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group,benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, orindazolyl group (these groups may be substituted with one of T¹ or twoor more of the same or different T¹, and bind to A⁶ at an arbitraryposition on the ring), R⁴ and R⁶ independently represent hydrogen atomor a lower alkyl group having 1 to 4 carbon atoms, R⁵ and R⁷independently represent hydrogen atom, a lower alkyl group having 1 to 4carbon atoms, or -A⁶-Qa, R⁸ is a lower alkyl group having 1 to 4 carbonatoms, R⁶′ has the same meaning as R⁶, or binds to R⁶ to form a 3- to6-membered ring together with the nitrogen atom to which they bind toform a saturated nitrogen-containing cycloalkyl group or morpholinogroup, p in Rc is an integer of 2 to 4, A⁴ is a single bond or methyleneor ethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, analkyl group having 1 to 8 carbon atoms, or Qa, Re is an alkyl grouphaving 1 to 8 carbon atoms, -A⁶-Qa, —(CH₂)_(i)R¹⁴, —OR²⁸, —SR²⁸, or—N(R²⁹)(R³⁰), i is an integer of 1 to 3, R¹⁴ is hydroxyl group, analkoxy group having 1 to 4 carbon atoms, carboxyl group, or anN,N-dialkylcarbamoyl group having 1 to 4 carbon atoms, R²⁸ is an alkylgroup having 1 to 8 carbon atoms or -A⁶-Qa, R²⁹ is an alkyl group having1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms,or -A⁶-Qa group, R³⁰ is hydrogen atom or a lower alkyl group having 1 to4 carbon atoms, or binds to R²⁹ to form a 3- to 6-membered ring togetherwith the nitrogen atom to which they bind to form a saturatednitrogen-containing cycloalkyl group or morpholino group, Rz has thesame meaning as Rx, or is -A⁵-Re, and Ry is hydrogen atom, an alkylgroup having 1 to 8 carbon atoms, or -A⁶-Qp, or binds to Rz to form asaturated or unsaturated nitrogen-containing cyclic substituent having 3to 7 atoms together with nitrogen atom to which they binds.(9) The compound or salt thereof according to any one of (1) to (8)mentioned above, wherein, in the formula (I), among C², C³, C⁴, C⁵, andC⁶ in the aromatic ring (E), one ring-constituting atom to which Rs orAR does not bind is replaced with nitrogen atom.(10) The compound or salt thereof according to any one of (1) to (8)mentioned above, wherein, in the formula (I), among C², C³, C⁴, C⁵, orC⁶ in the aromatic ring (E), one ring-constituting atom to which Rs orAR does not bind is replaced with —N(Rn¹)(Rn²) (provided that one of Rn¹and Rn² represents a substituent other than hydrogen atom).(11) The compound or salt thereof according to (1) or (10) mentionedabove, wherein, in the formula (I), Rs is —O-Rx.(12) The compound or salt thereof according to any one of (1) to (11)mentioned above, wherein, in the formula (I), Rs is —O-Rc.(13) The compound or salt thereof according to any one of (1) to (10)mentioned above, wherein, in the formula (I), Rs is —N(Ry)(Rz).(14) The compound or salt thereof according to any one of (1) to (10)mentioned above, wherein, in the formula (I), Rs is -D-Rx, and D is asingle bond, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—.(15) The compound or salt thereof according to any one of (1) to (10)mentioned above, wherein, in the formula (I), Rs is —S-Rx.(16) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), AR binds at the position of C² in thearomatic ring (E), and Rs binds to one of the ring-constituting carbonatoms C³, C⁴, and C⁵.(17) The compound or salt thereof according to (16) mentioned above,wherein, in the formula (I), Rs is —O-Rx, and no ring-constitutingcarbon atom in the aromatic ring (E) is replaced with V.(18) The compound or salt thereof according to (16) or (17) mentionedabove, wherein, in the formula (I), n is an integer of 2, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(19) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds at the position of C² in the aromatic ring (E), Rs binds to oneof ring-constituting carbon atoms C³, C⁴ and C⁵, Rs is —O-Rx, Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, and allof C², C³, C⁴, C⁵, and C⁶ in the aromatic ring (E) are not replaced withV.(20) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds at the position of C² in the aromatic ring (E), Rs binds to oneof ring-constituting carbon atoms C³, C⁴ and C⁵, Rs is —O-Rx, Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, and allof C², C³, C⁴, C⁵, and C⁶ in the aromatic ring (E) are not replaced withV.(21) The compound or salt thereof according to any one of (16) to (20)mentioned above, wherein, in the formula (I), Xa which may substitute onAR is methyl group, ethyl group, propyl group, hydroxyethyl group,carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxygroup, amino group, methylamino group, dimethylamino group, carboxylgroup, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoylgroup, or N,N-dimethylsulfamoyl group.(22) The compound or salt thereof according to any one of (16) to (21)mentioned above, wherein, in the formula (I), Rs is —O-Rx, Rx is butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethylgroup, or Rb (provided that Q in Rb is phenyl group or indan-2-ylgroup), A¹ is a single bond, a methylene group substituted with methylgroup or ethyl group, or unsubstituted methylene group, or an ethylenegroup substituted with methyl group or ethyl group, or unsubstitutedethylene group, A² is a single bond, oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)- (provided that when A² represents oxygenatom, sulfur atom, —N(methyl)-, or —N(ethyl)-, A¹ represents ethylene),and R² and R³ independently represent hydrogen atom, methyl group,fluorine atom, chlorine atom, trifluoromethyl group, methoxy group, ordimethylamino group (provided that when Q is phenyl group, A¹ is asingle bond or unsubstituted methylene, and A² is a single bond, one ofR² and R³ is a substituent other than hydrogen atom).(23) The compound or salt thereof according to any one of (16) to (22)mentioned above, wherein, in the formula (I), Rx-D- binds at theposition of C³ in the aromatic ring (E).(24) The compound or salt thereof according to any one of (16) to (22)mentioned above, wherein, in the formula (I), Rx-D- binds at theposition of C⁴ in the aromatic ring (E).(25) The compound or salt thereof according to any one of (16) to (22)mentioned above, wherein, in the formula (I), Rx-D- binds at theposition of C⁵ in the aromatic ring (E).(26) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 1 to 3, AR binds to C²,Rs binds to one of the ring-constituting carbon atoms C³, C⁴, and C⁵, aring-constituting atom among C³, C⁴, and C⁶ to which Rs does not bindmay be replaced with V,

V is nitrogen atom or carbon atom substituted with Zx, Zx is fluorineatom, chlorine atom, bromine atom, nitro group, methyl group, hydroxylgroup, methoxy group, amino group, N-methylamino group, N-ethylaminogroup, N-propylamino group, N-isopropylamino group, N,N-dimethylaminogroup, N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylaminogroup,

Rs is -D-Rx or —N(Ry)(Rz), D is oxygen atom or sulfur atom, Rx is butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethylgroup, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb orRc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group,oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group,indolyl group, or dihydrobenzodioxyl group, and A² is a single bond,oxygen atom, sulfur atom, —N(methyl)-, or —N(ethyl)-(provided that whenA² is oxygen atom, sulfur atom, —N(methyl)-, or —N(ethyl)-, A¹represents ethylene). R² and R³ independently represent hydrogen atom,methyl group, fluorine atom, chlorine atom, trifluoromethyl group,methoxy group, dimethylamino group, acetylamino group, ormethylsulfonylamino group (provided that when Q is phenyl group, A¹ is asingle bond or unsubstituted methylene, and A² is a single bond, one ofR² and R³ is a substituent other than hydrogen atom). Symbol p in Rc isan integer of 2 or 3, A⁴ is a single bond or methylene, A⁵ is —C(O)—,—C(S)—, or —S(O)₂—, Rd is hydrogen atom, or methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re ismethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group,cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group,phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenylgroup, phenylmethyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group,pyridin-4-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-ylgroup, thiophen-3-yl group, methoxy group, ethoxy group, propyloxygroup, isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxygroup, cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group,cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group,4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxygroup, thiomethoxy group, amino group, N-methylamino group,N,N-dimethylamino group, N-ethylamino group, N,N-diethylamino group,N-propylamino group, N-isopropylamino group, N-butylamino group,N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group,N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,or ethyloxycarbonylamino group,

Rz is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentylgroup, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group,cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group,2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group,2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group,indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry is hydrogen atom, methyl group, ethyl group, or isobutylgroup, or binds to Rz to form pyrrolidino group, piperidino group,piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-ylgroup, or pyrazol-1-yl group together with nitrogen atom to which theybinds,

AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), Xa is oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and Y is hydrogen atom, methylgroup or ethyl group.

(27) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C² is carbon atom to which AR binds, C³ is carbon atom to which Rsbinds, C⁴ may be replaced with V, C⁵ and C⁶ are unsubstitutedring-constituting carbon atoms,

V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorineatom, methyl group, hydroxyl group, amino group, N-methylamino group, orN,N-dimethylamino group,

Rs is —O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(28) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C² is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ may be replaced with V, C³ and C⁶ represents an unsubstitutedring-constituting carbon atom,

V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorineatom, methyl group, hydroxyl group, amino group, N-methylamino group, orN,N-dimethylamino group,

Rs is —O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(29) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), AR binds to C³ in the aromatic ring (E),and Rs binds to C⁵ or C⁶ in the aromatic ring (E).(30) The compound or salt thereof according to (29) mentioned above,wherein, in the formula (I), Rs is —O-Rx, and all of C², C³, C⁴, C⁵, andC⁶ in the aromatic ring (E) are not replaced with V.(31) The compound or salt thereof according to (29) or (30) mentionedabove, wherein, in the formula (I), n is an integer of 2, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(32) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to thering-constituting carbon atom C⁵ or C⁶ in the aromatic ring (E), Rs is—O-Rx, Y is hydrogen atom or a lower alkyl group having 1 to 4 carbonatoms, and all of C², C³, C⁴, C⁵, and C⁶ in the aromatic ring (E) arenot replaced with V.(33) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), n is an integer of 2, AR binds to C³ in thearomatic ring (E), Rs binds to the ring-constituting carbon atom C⁵ orC⁶ in the aromatic ring (E), Rs is —O-Rx, Y is hydrogen atom or a loweralkyl group having 1 to 4 carbon atoms, and all of C², C³, C⁴, C⁵, andC⁶ in the aromatic ring (E) are not replaced with V.(34) The compound or salt thereof according to any one of (29) to (33)mentioned above, wherein, in the formula (I), Xa which may substitute onAR is methyl group, ethyl group, propyl group, hydroxyethyl group,carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxygroup, amino group, methylamino group, dimethylamino group, carboxylgroup, carbamoyl group, acetyl group., methanesulfonyl group, sulfamoylgroup, or N,N-dimethylsulfamoyl group.(35) The compound or salt thereof according to any one of (29) to (34)mentioned above, wherein, in the formula (I), Rs is —O-Rx, Rx is butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethylgroup, or Rb (provided that Q in Rb is phenyl group or indan-2-ylgroup), A¹ is a single bond, or methylene group substituted with methylgroup or ethyl group or unsubstituted methylene group, or ethylene groupsubstituted with methyl group or ethyl group or unsubstituted ethylenegroup, A² is a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² is oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ is ethylene), and R² and R³ independentlyrepresent hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, or dimethylamino group (providedthat when Q is phenyl group, A¹ is a single bond or unsubstitutedmethylene, and A² is a single bond, one of R² and R³ is a substituentother than hydrogen atom).(36) The compound or salt thereof according to any one of (29) to (35)mentioned above, wherein, in the formula (I), R⁵ binds at the positionof C⁵ in the aromatic ring (E).(37) The compound or salt thereof according to any one of (29) to (35)mentioned above, wherein, in the formula (I), Rs binds at the positionof C⁶ in the aromatic ring (E).(38) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C³ is carbon atom to which AR binds, C⁶ is carbon atom to which Rsbinds, C², C⁴ and C⁶ are unsubstituted ring-constituting carbon atoms,

Rs is —O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(39) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), AR binds to C³ in the aromatic ring (E), Rsbinds to C⁴ in the aromatic ring (E), and C⁶ is replaced with V.(40) The compound or salt thereof according to (39) mentioned above,wherein, in the formula (I), n is an integer of 2, V is carbon atomsubstituted with Zx, Rs is —O-Rx, and Y is hydrogen atom or a loweralkyl group having 1 to 4 carbon atoms.(41) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁶ is carbon atom substituted with Zx, Rs is —O-Rx, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(42) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁶ is carbon atom substituted with Zx, Rs is —O-Rx, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(43) The compound or salt thereof according to any one of (39) to (42)mentioned above, wherein, in the formula (I), Xa which may substitute onAR is methyl group, ethyl group, propyl group, hydroxyethyl group,carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxygroup, amino group, methylamino group, dimethylamino group, carboxylgroup, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoylgroup, or N,N-dimethylsulfamoyl group.(44) The compound or salt thereof according to any one of (39) to (43)mentioned above, wherein, in the formula (I), Rs is —O-Rx, Rx is butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethylgroup, or Rb (provided that Q in Rb is phenyl group or indan-2-ylgroup), A¹ is a single bond, or methylene group substituted with methylgroup or ethyl group or unsubstituted methylene group, or ethylene groupsubstituted with methyl group or ethyl group or unsubstituted ethylenegroup, A² is a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² is oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ is ethylene), R² and R³ independentlyrepresent hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, or dimethylamino group (providedthat when Q is phenyl group, A¹ is a single bond or unsubstitutedmethylene, and A² is a single bond, one of R² and R³ is a substituentother than hydrogen atom).(45) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁶ is carbon atom substituted with Zx, C² and C⁶ areunsubstituted ring-constituting carbon atoms,

Zx is fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group,

Rs is —O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl, group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(46) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), AR binds to C³ in the aromatic ring (E), Rsbinds to C⁴ in the aromatic ring (E), C⁵ is nitrogen atom, and C² and C⁶are unsubstituted ring-constituting carbon atoms.(47) The compound or salt thereof according to (46) mentioned above,wherein, in the formula (I), n is an integer of 2, D is oxygen atom, andY is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(48) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is nitrogen atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is —O-Rx, and Y is hydrogen atom or alower alkyl group having 1 to 4 carbon atoms.(49) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is nitrogen atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is —O-Rx, and Y is hydrogen atom or alower alkyl group having 1 to 4 carbon atoms.(50) The compound or salt thereof according to any one of (46) to (49)mentioned above, wherein, in the formula (I), Xa which may substitute onAR is methyl group, ethyl group, propyl group, hydroxyethyl group,carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxygroup, amino group, methylamino group, dimethylamino group, carboxylgroup, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoylgroup, or N,N-dimethylsulfamoyl group.(51) The compound or salt thereof according to any one of (46) to (50)mentioned above, wherein, in the formula (I), Rs is —O-Rx, Rx is butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethylgroup, or Rb (provided that Q in Rb is phenyl group or indan-2-ylgroup), A¹ is a single bond, or methylene group substituted with methylgroup or ethyl group or unsubstituted methylene group, or ethylene groupsubstituted with methyl group or ethyl group or unsubstituted ethylenegroup, A² is a single bond, oxygen atom, sulfur atom, —N(methyl)- or—N(ethyl)- (provided that when A² is oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ is ethylene), and R² and R³ independentlyrepresent hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, or dimethylamino group (providedthat when Q is phenyl group, A¹ is a single bond or unsubstitutedmethylene, and A² is a single bond, one of R² and R³ is a substituentother than hydrogen atom).(52) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ is nitrogen atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms,

Rs is —O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(53) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), AR binds to C³ in the aromatic ring (E), Rsbinds to C⁴ in the aromatic ring (E), C⁵ is a ring-constituting carbonatom substituted with Zx, or an unsubstituted ring-constituting carbonatom, C² and C⁶ are unsubstituted ring-constituting carbon atoms, Rs is-D-Rx, and D is a single bond, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—.(53-2) The compound of salt thereof according to (1-2) mentioned above,wherein, in the formula (I), AR binds to C³ in the aromatic ring (E), Rsbinds to C⁴ in the aromatic ring (E), C⁵ is nitrogen atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is -D-Rx, and D is asingle bond, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—.(53-3) The compound or salt thereof according to (53) or (53-2)mentioned above, wherein, in the formula (I), Rs is -D-Rx and D issingle bond.(54) The compound or salt thereof according to any one of (53) to (53-3)mentioned above, wherein, in the formula (I), n is an integer of 2, andY is hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(55) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is a ring-constituting carbon atom substituted with Zx, oran unsubstituted ring-constituting carbon atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is -D-Rx, D is a singlebond, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—, and Y is hydrogen atom ora lower alkyl group having 1 to 4 carbon atoms.(55-2) The compound or a salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ may be replaced with V, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is -D-Rx, D is a single bond, and Yis hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(56) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁶ is a ring-constituting carbon atom substituted with Zx, oran unsubstituted ring-constituting carbon atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is -D-Rx, D is a singlebond, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—, and Y is hydrogen atom ora lower alkyl group having 1 to 4 carbon atoms.(56-2) The compound or a salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ may be replaced with V, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is -D-Rx, D is a single bond, and Yis hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(57) The compound or salt thereof according to any one of (53) to (56-2)mentioned above, wherein, in the formula (I), Xa which may substitute onAR is methyl group, ethyl group, propyl group, hydroxyethyl group,carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxygroup, amino group, methylamino group, dimethylamino group, carboxylgroup, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoylgroup, or N,N-dimethylsulfamoyl group.(58) The compound or salt thereof according to any one of (53) to (57)mentioned above, wherein, in the formula (I), Rs is -D-Rx, Rx is butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethylgroup, or Rb (provided that Q in Rb is phenyl group or indan-2-ylgroup), A¹ is a single bond, or methylene group substituted with methylgroup or ethyl group or unsubstituted methylene group, or ethylene groupsubstituted with methyl group or ethyl group or unsubstituted ethylenegroup, A² is a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² represents oxygen atom, sulfur atom,—N(methyl)- or —N(ethyl)-, A¹ represents ethylene), and R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, or dimethylaminogroup (provided that when Q is phenyl group, A¹ is a single bond orunsubstituted methylene, and A² is a single bond, one of R² and R³ is asubstituent other than hydrogen atom).(58-2) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 1 to 3, AR binds to C³in the aromatic ring (E), Rs binds to C⁴ in the aromatic ring (E), C⁵may be replaced with V, C² and C⁶ are unsubstituted ring-constitutingcarbon atoms, V is nitrogen atom or V is carbon atom substituted withZx, Zx is any one of fluorine atom, methyl group, hydroxyl group, aminogroup, N-methylamino group, or N,N-dimethylamino group,

Rs is -D-Rx, D is a single bond, Rx is butyl group, isobutyl group,2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, cyclopentylmethyl group, cyclohexylmethyl group,2-cyclopentylethyl group, or 2-cyclohexylethyl group, or Rx is Rb or Rc(provided that Q in Rb is phenyl group, thienyl group, furyl group,pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group,indanyl group, indolyl group, or dihydrobenzodioxyl group), A² is asingle bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)-(provided that when A² represents oxygen atom, sulfur atom,—N(methyl)- or —N(ethyl)-, A¹ represents ethylene), R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group, (provided thatwhen Q is phenyl group, A¹ is a single bond or unsubstituted methylene,and A² is a single bond, one of R² and R³ is a substituent other thanhydrogen atom). p in Rc is an integer of 2 or 3, A⁴ is a single bond ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, methoxy group, ethoxygroup, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxygroup, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group,cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxygroup, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxygroup, 4-fluorophenyloxy group, thiomethoxy group, amino group,N-methylamino group, N,N-dimethylamino group, N-ethylamino group,N,N-diethylamino group, N-propylamino group, N-isopropylamino group,N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylaminogroup,

AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), Xa is oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(58-3) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2, AR binds to C³ in thearomatic ring (E), Rs binds to C⁴ in the aromatic ring (E), C⁵ may bereplaced with V, C² and C⁶ are unsubstituted ring-constituting carbonatoms, V is nitrogen atom or V is carbon atom substituted with Zx, Zx isany one of fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group,

Rs is -D-Rx, D is a single bond, Rx is butyl group, isobutyl group,2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group,2,3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenylgroup, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenylgroup, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, 2,3-difluorophenyl group,2,4-difluorophenyl group, 2,5-difluorophenyl group, 3,4-difluorophenylgroup, 2,3-dichlorophenyl group, 2,4-dichlorophenyl group,2,5-dichlorophenyl group, 2,6-dichlorophenyl group, 3,4-dichlorophenylgroup, 3,5-dichlorophenyl group, 2-trifluoromethylphenyl group,3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group,4-(N,N-dimethylamino)phenyl group, indan-2-yl group, 4-methylindan-2-ylgroup, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group,thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group,pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group,naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-1H-indol-5-ylgroup, 1H-indazol-5-yl group, 1-methyl-1H-indazol-5-yl group,biphenyl-2-yl group, biphenyl 3-yl group, biphenyl-4-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(58-4) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2, AR binds to C³ in thearomatic ring (E), Rs binds to C⁴ in the aromatic ring (E), C⁵ may bereplaced with V, C² and C⁶ are unsubstituted ring-constituting carbonatoms,

V is nitrogen atom or V is carbon atom substituted with Zx, Zx is anyone of fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group,

Rs is -D-Rx, D is a single bond, Rx is phenyl group, 2-methylphenylgroup, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenylgroup, 3,5-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenylgroup, 4-methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenylgroup, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, 2,3-difluorophenyl group, 2,4-difluorophenylgroup, 2,5-difluorophenyl group, 3,4-difluorophenyl group,2,3-dichlorophenyl group, 2,4-dichlorophenyl group, 2,5-dichlorophenylgroup, 2,6-dichlorophenyl group, 3,4-dichlorophenyl group,3,5-dichlorophenyl group, 2-trifluoromethylphenyl group,3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group,4-(N,N-dimethylamino)phenyl group, indan-2-yl group, 4-methylindan-2-ylgroup, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group,thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group,pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group,naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-1H-indol-5-ylgroup, 1H-indazol-5-yl group, or 1-methyl-1H-indazol-5-yl group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(58-5) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2, AR binds to C³ in thearomatic ring (E),

Rs binds to C⁴ in the aromatic ring (E), C², C⁵, and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is -D-Rx, D is a singlebond, Rx is phenyl group, 2-methylphenyl group, 3-methylphenyl group,4-methylphenyl group, 2,3-dimethylphenyl group, 3,5-dimethylphenylgroup, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenylgroup, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group,2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group,2,3-difluorophenyl group, 2,4-difluorophenyl group, 2,5-difluorophenylgroup, 3,4-difluorophenyl group, 2,3-dichlorophenyl group,2,4-dichlorophenyl group, 2,5-dichlorophenyl group, 2,6-dichlorophenylgroup, 3,4-dichlorophenyl group, 3,5-dichlorophenyl group,2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group,4-trifluoromethylphenyl group, 4-(N,N-dimethylamino)phenyl group,indan-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-ylgroup, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group,pyridin-4-yl group, naphthalen-1-yl group, naphthalen-2-yl group,1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1H-indazol-5-ylgroup, or 1-methyl-1H-indazol-5-yl group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and Y is hydrogen atom, methyl group, or ethylgroup.

(59) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 1 to 3,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ may be replaced with V, C² and C⁶ are unsubstitutedring-constituting carbon atoms,

V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorineatom, chlorine atom, bromine atom, nitro group, methyl group, hydroxylgroup, methoxy group, amino group, N-methylamino group, N-ethylaminogroup, N-propylamino group, N-isopropylamino group, N,N-dimethylaminogroup, N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylaminogroup,

Rs is —S-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group,thienyl group, furyl group, pyridyl group, oxazolyl group, naphthylgroup, tetrahydronaphthyl group, indanyl group, indolyl group, ordihydrobenzodioxyl group, A² is a single bond, oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)- (provided that when A² is oxygen atom, sulfuratom, —N(methyl)-, or —N(ethyl)-, A¹ is ethylene), R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q is phenyl group, A¹ is a single bond or unsubstituted methylene,and A² is a single bond, one of R² and R³ is a substituent other thanhydrogen atom), p in Rc is an integer of 2 or 3, A⁴ is a single bond ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, methoxy group, ethoxygroup, propyloxy group, isopropyloxy group, butyloxy group, isobutyloxygroup, t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group,cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxygroup, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxygroup, 4-fluorophenyloxy group, thiomethoxy group, amino group,N-methylamino group, N,N-dimethylamino group, N-ethylamino group,N,N-diethylamino group, N-propylamino group, N-isopropylamino group,N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylaminogroup,

AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), Xa is oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(59-2) The compound or salt thereof according to (1) mentioned above,wherein, in the formula (I), AR binds to C³ in the aromatic ring (E), Rsbinds to C⁴ in the aromatic ring (E), C⁵ is a ring-constituting carbonatom substituted with Zx, or an unsubstituted ring-constituting carbonatom, C² and C⁶ are unsubstituted ring-constituting carbon atoms, and Rsis —N(Ry)(Rz).(59-3) The compound or salt thereof according to (1) mentioned above,wherein, in the formula (I), AR binds to C³ in the aromatic ring (E), Rsbinds to C⁴ in the aromatic ring (E), C⁵ is nitrogen atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, and Rs is —N(Ry)(Rz).(60) The compound or salt thereof according to (59-2) or (59-3)mentioned above, wherein, in the formula (I), Link is —(CH₂)_(n)—, n isan integer of 2, and Y is hydrogen atom or a lower alkyl group having 1to 4 carbon atoms.(61) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is a ring-constituting carbon atom substituted with Zx, oran unsubstituted ring-constituting carbon atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is —N(Ry)(Rz), and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(61-2) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is nitrogen atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is —N(Ry)(Rz), and Y is hydrogen atomor a lower alkyl group having 1 to 4 carbon atoms.(62) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is a ring-constituting carbon atom substituted with Zx, oran unsubstituted ring-constituting carbon atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is —N(Ry)(Rz), and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(62-2) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is nitrogen atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is —N(Ry)(Rz), and Y is hydrogen atomor a lower alkyl group having 1 to 4 carbon atoms.(63) The compound or salt thereof according to any one of (59-2) to(62-2) mentioned above, wherein, in the formula (I), Xa which maysubstitute on AR is methyl group, ethyl group, propyl group,hydroxyethyl group, carboxymethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, amino group, methylamino group, dimethylaminogroup, carboxyl group, carbamoyl group, acetyl group, methanesulfonylgroup, sulfamoyl group, or N,N-dimethylsulfamoyl group.(64) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 1 to 3, C³ is carbonatom to which AR binds, C⁴ is carbon atom to which Rs binds, C², C⁵, andC⁶ are unsubstituted ring-constituting carbon atoms,

Rs is —N(Ry)(Rz), Rz is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2 (2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group,or binds to Rz to form pyrrolidino group, piperidino group, piperazinogroup, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, orpyrazol-1-yl group together with the nitrogen atom to which they bind,

AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (these groups may be substituted with one of Xa or two or more ofthe same or different Xa),

Xa represents oxo group, thioxo group, fluorine atom, chlorine atom,trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(65) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C², C⁵ and C⁶ are unsubstituted ring-constituting carbon atoms,

Rs is —N(Ry)(Rz), Rz is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group,or binds to Rz to form pyrrolidino group, piperidino group, ormorpholino group together with the nitrogen atom to which they bind,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group

(65-2) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C², C⁵ and C⁶ are unsubstituted ring-constituting carbon atoms,

Rs is —N(Ry)(Rz), and the group represented by —N(Ry)(Rz) isN,N-dimethylamino group, N-ethyl-N-methylamino group, N,N-diethylaminogroup, N-methyl-N-propylamino group, N-ethyl-N-propylamino group,N-isopropyl-N-methylamino group, N-ethyl-N-isopropylamino group,N-butylamino group, N-butyl-N-methylamino group, N-butyl-N-ethylaminogroup, N-isobutylamino group, N-isobutyl-N-methylamino group,N-ethyl-N-isobutylamino group, N-(2-ethylbutyl)amino group,N-(2-ethylbutyl)-N-methylamino group, N-cyclopentylamino group,N-cyclopentyl-N-methylamino group, N-cyclohexylamino group,N-cyclohexyl-N-methylamino group, N-cycloheptylamino group,N-(cyclopentylmethyl)amino group, N-(cyclopentylmethyl)-N-methylaminogroup, N-(cyclohexylmethyl)amino group,N-(cyclohexylmethyl)-N-methylamino group, N-(2-methylphenyl)amino group,N-(4-methylphenyl)amino group, N-(2-fluorophenyl)amino group,N-(3-fluorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(2-chlorophenyl)amino group, N-(3-chlorophenyl)amino group,N-(4-chlorophenyl)amino group, N-(indan-2-yl)amino group,N-(1-phenylethyl)amino group, N-[1-(2-fluorophenyl)ethyl]amino group,N-[1-(3-fluorophenyl)ethyl]amino group, N-[1-(4-fluorophenyl)ethyl]aminogroup, N-[1-(2-chlorophenyl)ethyl]amino group,N-[1-(3-chlorophenyl)ethyl]amino group, N-[1-(4-chlorophenyl)ethyl]aminogroup, N-(2-methylphenylmethyl)amino group,N-methyl-N-(2-methylphenylmethyl)amino group,N-(3-methylphenylmethyl)amino group,N-methyl-N-(3-methylphenylmethyl)amino group,N-(4-methylphenylmethyl)amino group,N-methyl-N-(4-methylphenylmethyl)amino group,N-(2-fluorophenylmethyl)amino group,N-(2-fluorophenylmethyl)-N-methylamino group,N-(3-fluorophenylmethyl)amino group,N-(3-fluorophenylmethyl)-N-methylamino group,N-(4-fluorophenylmethyl)amino group,N-(4-fluorophenylmethyl)-N-methylamino group,N-(2-chlorophenylmethyl)amino group,N-(2-chlorophenylmethyl)-N-methylamino group,N-(3-chlorophenylmethyl)amino group,N-(3-chlorophenylmethyl)-N-methylamino group,N-(4-chlorophenylmethyl)amino group,N-(4-chlorophenylmethyl)-N-methylamino group,N-(2,3-difluorophenylmethyl)amino group,N-(2,3-difluorophenylmethyl)-N-methylamino group,N-(2,4-difluorophenylmethyl)amino group,N-(2,4-difluorophenylmethyl)-N-methylamino group,N-(2,5-difluorophenylmethyl)amino group,N-(2,5-difluorophenylmethyl)-N-methylamino group,N-(3,4-difluorophenylmethyl)amino group,N-(3,4-difluorophenylmethyl)-N-methylamino group,N-(3,5-difluorophenylmethyl)amino group,N-(3,5-difluorophenylmethyl)-N-methylamino group,N-(2,3-dichlorophenylmethyl)amino group,N-(2,3-dichlorophenylmethyl)-N-methylamino group,N-(2,4-dichlorophenylmethyl)amino group,N-(2,4-dichlorophenylmethyl)-N-methylamino group,N-(2,5-dichlorophenylmethyl)amino group,N-(2,5-dichlorophenylmethyl)-N-methylamino group,N-(2,6-dichlorophenylmethyl)amino group,N-(2,6-dichlorophenylmethyl)-N-methylamino group,N-(3,4-dichlorophenylmethyl)amino group,N-(3,4-dichlorophenylmethyl)-N-methylamino group,N-(3,5-dichlorophenylmethyl)amino group,N-(3,5-dichlorophenylmethyl)-N-methylamino group,N-[2-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[2-(trifluoromethyl)phenylmethyl]amino group,N-[3-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[3-(trifluoromethyl)phenylmethyl]amino group,N-[4-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[4-(trifluoromethyl)phenylmethyl]amino group, 1-pyrrolidinogroup, 1-(4-methylpiperidino) group, 1-homopiperidino group, or4-morpholino group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(65-3) The compound or salt thereof according to (1) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ is nitrogen atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms,

Rs is —N(Ry)(Rz), and the group represented by —N(Ry)(Rz) isN,N-dimethylamino group, N-ethyl-N-methylamino group, N,N-diethylaminogroup, N-methyl-N-propylamino group, N-ethyl-N-propylamino group,N-isopropyl-N-methylamino group, N-ethyl-N-isopropylamino group,N-butylamino group, N-butyl-N-methylamino group, N-butyl-N-ethylaminogroup, N-isobutylamino group, N-isobutyl-N-methylamino group,N-ethyl-N-isobutylamino group, N-(2-ethylbutyl)amino group,N-(2-ethylbutyl)-N-methylamino group, N-cyclopentylamino group,N-cyclopentyl-N-methylamino group, N-cyclohexylamino group,N-cyclohexyl-N-methylamino group, N-cycloheptylamino group,N-(cyclopentylmethyl)amino group, N-(cyclopentylmethyl)-N-methylaminogroup, N-(cyclohexylmethyl)amino group,N-(cyclohexylmethyl)-N-methylamino group, N-(2-methylphenyl)amino group,N-(4-methylphenyl)amino group, N-(2-fluorophenyl)amino group,N-(3-fluorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(2-chlorophenyl)amino group, N-(3-chlorophenyl)amino group,N-(4-chlorophenyl)amino group, N-(indan-2-yl)amino group,N-(1-phenylethyl)amino group, N-[1-(2-fluorophenyl)ethyl]amino group,N-[1-(3-fluorophenyl)ethyl]amino group, N-[1-(4-fluorophenyl)ethyl]aminogroup, N-[1-(2-chlorophenyl)ethyl]amino group,N-[1-(3-chlorophenyl)ethyl]amino group, N-[1-(4-chlorophenyl)ethyl]aminogroup, N-(2-methylphenylmethyl)amino group,N-methyl-N-(2-methylphenylmethyl)amino group,N-(3-methylphenylmethyl)amino group,N-methyl-N-(3-methylphenylmethyl)amino group,N-(4-methylphenylmethyl)amino group,N-methyl-N-(4-methylphenylmethyl)amino group,N-(2-fluorophenylmethyl)amino group,N-(2-fluorophenylmethyl)-N-methylamino group,N-(3-fluorophenylmethyl)amino group,N-(3-fluorophenylmethyl)-N-methylamino group,N-(4-fluorophenylmethyl)amino group,N-(4-fluorophenylmethyl)-N-methylamino group,N-(2-chlorophenylmethyl)amino group,N-(2-chlorophenylmethyl)-N-methylamino group,N-(3-chlorophenylmethyl)amino group,N-(3-chlorophenylmethyl)-N-methylamino group,N-(4-chlorophenylmethyl)amino group,N-(4-chlorophenylmethyl)-N-methylamino group,N-(2,3-difluorophenylmethyl)amino group,N-(2,3-difluorophenylmethyl)-N-methylamino group,N-(2,4-difluorophenylmethyl)amino group,N-(2,4-difluorophenylmethyl)-N-methylamino group,N-(2,5-difluorophenylmethyl)amino group,N-(2,5-difluorophenylmethyl)-N-methylamino group,N-(3,4-difluorophenylmethyl)amino group,N-(3,4-difluorophenylmethyl)-N-methylamino group,N-(3,5-difluorophenylmethyl)amino group,N-(3,5-difluorophenylmethyl)-N-methylamino group,N-(2,3-dichlorophenylmethyl)amino group,N-(2,3-dichlorophenylmethyl)-N-methylamino group,N-(2,4-dichlorophenylmethyl)amino group,N-(2,4-dichlorophenylmethyl)-N-methylamino group,N-(2,5-dichlorophenylmethyl)amino group,N-(2,5-dichlorophenylmethyl)-N-methylamino group,N-(2,6-dichlorophenylmethyl)amino group,N-(2,6-dichlorophenylmethyl)-N-methylamino group,N-(3,4-dichlorophenylmethyl)amino group,N-(3,4-dichlorophenylmethyl)-N-methylamino group,N-(3,5-dichlorophenylmethyl)amino group,N-(3,5-dichlorophenylmethyl)-N-methylamino group,N-[2-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[2-(trifluoromethyl)phenylmethyl]amino group,N-[3-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[3-(trifluoromethyl)phenylmethyl]amino group,N-[4-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[4-(trifluoromethyl)phenylmethyl]amino group, 1-pyrrolidinogroup, 1-(4-methylpiperidino) group, 1-homopiperidino group, or4-morpholino group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(66) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2, AR binds to C³ in thearomatic ring (E), Rs binds to C⁴ in the aromatic ring (E), C⁵ is carbonatom substituted with —N(Rn¹)(Rn²) (provided that one of Rn¹ and Rn² isa substituent other than hydrogen atom), C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is —O-Rx, and Y is hydrogen atom or alower alkyl group having 1 to 4 carbon atoms.(67) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is carbon atom substituted with —N(Rn¹)(Rn²) (provided thatone of Rn¹ and Rn² is a substituent other than hydrogen atom), C² and C⁶are unsubstituted ring-constituting carbon atoms, Rs is —O-Rx, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(68) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is carbon atom substituted with —N(Rn¹)(Rn²) (provided thatone of Rn¹ and Rn² is a substituent other than hydrogen atom), C² and C⁶are unsubstituted ring-constituting carbon atoms, Rs is —O-Rx, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(69) The compound or salt thereof according to any one of (66) to (68)mentioned above, wherein, in the formula (I), Xa which may substitute onAR is methyl group, ethyl group, propyl group, hydroxyethyl group,carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxygroup, amino group, methylamino group, dimethylamino group, carboxylgroup, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoylgroup, or N,N-dimethylsulfamoyl group.(70) The compound or salt thereof according to any one of (66) to (69)mentioned above, wherein, in the formula (I), Rs is —O-Rx, Rx is a groupselected from butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, and cyclohexylmethyl group, or Rb (providedthat Q in Rb is phenyl group or indan-2-yl group), A¹ is a single bond,or methylene group substituted with methyl group or ethyl group orunsubstituted methylene group, or ethylene group substituted with methylgroup or ethyl group or unsubstituted ethylene group, A² represents asingle bond, oxygen atom, sulfur atom, —N(methyl)-, or —N(ethyl)-(provided that when A² is oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)-, A¹ is ethylene), and R² and R³ independently representhydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, or dimethylamino group (providedthat when Q is phenyl group, A¹ is a single bond or unsubstitutedmethylene, and A² is a single bond, one of R² and R³ is a substituentother than hydrogen atom).(71) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ is carbon atom substituted with Zx, C² and C⁶ areunsubstituted ring-constituting carbon atoms,

Zx is N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, or N,N-dimethylsulfamoylamino group,

Rs is —O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(72) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2, AR binds to C³ in thearomatic ring (E), Rs binds to C⁴ in the aromatic ring (E), C⁵ is aring-constituting carbon atom substituted with Zx, or an unsubstitutedring-constituting carbon atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is -D-Rc, D is oxygen atom or sulfuratom, and Y is hydrogen atom or a lower alkyl group having 1 to 4 carbonatoms.(73) The compound or salt thereof according to (4) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is a ring-constituting carbon atom substituted with Zx, oran unsubstituted ring-constituting carbon atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is —O-Rc, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(74) The compound or salt thereof according to (5) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is a ring-constituting carbon atom substituted with Zx, oran unsubstituted ring-constituting carbon atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is —O-Rc, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(75) The compound or salt thereof according to any one of (72) to (74)mentioned above, wherein, in the formula (I), Xa which may substitute onAR is methyl group, ethyl group, propyl group, hydroxyethyl group,carboxymethyl group, hydroxyl group, methoxy group, 2-hydroxyethyloxygroup, amino group, methylamino group, dimethylamino group, carboxylgroup, carbamoyl group, acetyl group, methanesulfonyl group, sulfamoylgroup, or N,N-dimethylsulfamoyl group.(76) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 1 to 3,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ may be replaced with V, C² and C⁶ are unsubstitutedring-constituting carbon atoms,

V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorineatom, chlorine atom, bromine atom, nitro group, methyl group, hydroxylgroup, methoxy group, amino group, N-methylamino group, N-ethylaminogroup, N-propylamino group, N-isopropylamino group, N,N-dimethylaminogroup, N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylaminogroup,

Rs is -D-Rc, D is oxygen atom or sulfur atom, p in Rc is an integer of 2or 3, A⁴ is a single bond or methylene, A⁵ is —C(O)—, —C(S)—, or—S(O)₂—, Rd is hydrogen atom, or methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, cyclopropyl group,cyclopropylmethyl group, cyclopentyl group, cyclopentylmethyl group,cyclohexyl group, cyclohexylmethyl group, phenyl group, 4-methylphenylgroup, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, or pyridin-4-yl group, Re is methyl group,ethyl group, propyl group, isopropyl group, butyl group, isobutyl group,t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group,cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethylgroup, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-ylgroup, methoxy group, ethoxy group, propyloxy group, isopropyloxy group,butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxygroup, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxygroup, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxygroup, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxygroup, amino group, N-methylamino group, N,N-dimethylamino group,N-ethylamino group, N,N-diethylamino group, N-propylamino group,N-isopropylamino group, N-butylamino group, N-isobutylamino group,N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylaminogroup, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,or ethyloxycarbonylamino group,

AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), Xa is oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(77) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 2,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ may be replaced with V, C² and C⁶ are unsubstitutedring-constituting carbon atoms,

V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorineatom, chlorine atom, bromine atom, methyl group, hydroxyl group, methoxygroup, amino group, N-methylamino group, N-ethylamino group,N-propylamino group, N-isopropylamino group, N,N-dimethylamino group,N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylaminogroup,

Rs is —O-Rc, p in Rc is an integer of 2, A⁴ is a single bond ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is methyl group, ethylgroup, propyl group, isopropyl group, butyl group, isobutyl group,cyclopropyl group, cyclopentyl group, cyclohexyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, or 4-fluorophenylmethyl group, Re isisopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, propyloxy group,isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group,cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group,cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group,4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxygroup, N-propylamino group, N-isopropylamino group, N-butylamino group,N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group,N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, pyrrolidino group, piperidino group, ormorpholino group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(78) The compound or salt thereof according to (7) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, n is an integer of 2,AR binds to C³ in the aromatic ring (E), Rs binds to C⁴ in the aromaticring (E), C⁵ is a ring-constituting carbon atom substituted with Zx, oran unsubstituted ring-constituting carbon atom, C² and C⁶ areunsubstituted ring-constituting carbon atoms, Rs is —O-Rx, and Y ishydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.(79) The compound or salt thereof according to (78) mentioned above,wherein, in the formula (I), Xa which may substitute on AR is methylgroup, ethyl group, propyl group, hydroxyethyl group, carboxymethylgroup, hydroxyl group, methoxy group, 2-hydroxyethyloxy group, aminogroup, methylamino group, dimethylamino group, carboxyl group, carbamoylgroup, acetyl group, methanesulfonyl group, sulfamoyl group, orN,N-dimethylsulfamoyl group.(80) The compound or salt thereof according to (78) or (79) mentionedabove, wherein, in the formula (I), Rs is —O-Rx, Rx is butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, or cyclohexylmethyl group,or Rb (provided that Q in Rb is phenyl group or indan-2-yl group), A¹ isa single bond, or methylene group substituted with methyl group or ethylgroup or unsubstituted methylene group, or ethylene group substitutedwith methyl group or ethyl group or unsubstituted ethylene group, A² isa single bond, oxygen atom, sulfur atom, —N(methyl)-, or —N(ethyl)-(provided that when A² is oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)-, A¹ is ethylene), and R² and R³ independently representhydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, or dimethylamino group (providedthat when Q is phenyl group, A¹ is a single bond or unsubstitutedmethylene, and A² is a single bond, one of R² and R³ is a substituentother than hydrogen atom).(81) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 1 to 3,

C³ is carbon atom to which AR binds, C⁴ is carbon atom to which Rsbinds, C⁵ may be replaced with V, C² and C⁶ are unsubstitutedring-constituting carbon atoms,

V is nitrogen atom, or carbon atom substituted with Zx, Zx is fluorineatom, chlorine atom, bromine atom, nitro group, methyl group, hydroxylgroup, methoxy group, amino group, N-methylamino group, N-ethylaminogroup, N-propylamino group, N-isopropylamino group, N,N-dimethylaminogroup, N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylaminogroup,

Rs is —O-Rx, Rx is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or Rb or Rc, Q in Rb is phenyl group,thienyl group, furyl group, pyridyl group, oxazolyl group, naphthylgroup, tetrahydronaphthyl group, indanyl group, indolyl group, ordihydrobenzodioxyl group, A² is a single bond, oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)- (provided that when A² is oxygen atom, sulfuratom, —N(methyl)-, or —N(ethyl)-, A¹ is ethylene), R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q is phenyl group, A¹ is a single bond or unsubstituted methylene,and A² is a single bond, one of R² and R³ is a substituent other thanhydrogen atom), p in Rc is an integer of 2 or 3, A⁴ is a single bond ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylaminogroup,

AR is cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), Xa is oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(82) The compound or salt thereof according to (6) mentioned above,wherein, in the formula (I), Link is —(CH₂)_(n)—, AR binds to C³ in thearomatic ring (E), Rs binds to C⁴ in the aromatic ring (E), C⁵ is aring-constituting carbon atom substituted with Zx, or an unsubstitutedring-constituting carbon atom, C² and C⁶ are unsubstitutedring-constituting carbon atoms, Rs is —O-Rx, and Rx is a linear orbranched saturated alkyl group having 3 to 8 carbon atoms, or Ra or Rb.(83) The compound or salt thereof according to (82) mentioned above,wherein, in the formula (I), Zx is fluorine atom, chlorine atom, nitrogroup, amino group, methyl group, or OR⁹.(84) The compound or salt thereof according to (1-2) mentioned above,wherein, in the formula (I), n is an integer of 1 to 3, AR binds to C³,Rs binds to one of the ring-constituting atoms C⁴, C⁵, and C⁶, aring-constituting carbon atom to which Rs does not bind among C⁴, C⁵,and C⁶ may be replaced with V,

V is nitrogen atom or carbon atom substituted with Zx, Zx is fluorineatom, chlorine atom, bromine atom, nitro group, methyl group, hydroxylgroup, methoxy group, amino group, N-methylamino group, N-ethylaminogroup, N-propylamino group, N-isopropylamino group, N,N-dimethylaminogroup, N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylaminogroup,

Rs is -D-Rx or —N(Ry)(Rz), D is oxygen atom or sulfur atom, Rx is butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethylgroup, 2-cyclopentylethyl group, or 2-cyclohexylethyl group, or Rb orRc, Q in Rb is phenyl group, thienyl group, furyl group, pyridyl group,oxazolyl group, naphthyl group, tetrahydronaphthyl group, indanyl group,indolyl group, or dihydrobenzodioxyl group, A² is a single bind, oxygenatom, sulfur atom, —N(methyl)-, or —N(ethyl)-(provided that when A² isoxygen atom, sulfur atom, —N(methyl)-, or —N(ethyl)-, A¹ is ethylene),R² and R³ independently represent hydrogen atom, methyl group, fluorineatom, chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q is phenyl group, A¹ is a single bind or unsubstituted methylene,and A² is a single bind, one of R² and R³ is a substituent other thanhydrogen atom), p in Rc is an integer of 2 or 3, A⁴ is a single bind ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group or ethyloxycarbonylaminogroup, Rz is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group,or binds to Rz to form pyrrolidino group, piperidino group, piperazinogroup, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, orpyrazol-1-yl group together with the nitrogen atom,

AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-e]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), Xa is oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and

Y is hydrogen atom, methyl group, or ethyl group.

(85) A medicament containing a compound represented by theaforementioned formula (I) or a pharmacologically acceptable saltthereof as an active ingredient.(86) An agent for suppressing production of a prostaglandin and/orleukotriene, which contains a compound represented by the aforementionedformula (I) or a pharmacologically acceptable salt thereof as an activeingredient.(87) The medicament according to (85) for prophylactic and/ortherapeutic treatment of a disease caused by production of aprostaglandin and/or leukotriene.(88) The medicament according to (85) for prophylactic and/ortherapeutic treatment of an inflammatory disease of a mammal.(89) The medicament according to (85) for prophylactic and/ortherapeutic treatment of an autoimmune disease of a mammal.(90) The medicament according to (85) for prophylactic and/ortherapeutic treatment of an allergic disease of a mammal.(91) The medicament according to (85) for defervescence and/or painrelief of a mammal.(92) A pharmaceutical composition for prophylactic and/or therapeutictreatment of a condition of living body of a mammal exhibiting an acuteor chronic inflammatory reaction, which comprises a prophylacticallyand/or therapeutically effective amount of a compound represented by theaforementioned formula (I) or a pharmacologically acceptable saltthereof and a pharmaceutically acceptable carrier.(93) A method for prophylactic and/or therapeutic treatment of acondition of living body of a mammal exhibiting an acute or chronicinflammatory reaction, which comprises administering a prophylacticallyand/or therapeutically effective amount of a compound represented by theaforementioned formula (I) or a pharmacologically acceptable saltthereof to the mammal.(94) A compound represented by the following formula (II):

[In the formula, each of C²′, C³′, C⁴′, C⁵′, and C⁶′ in the aromaticring (E′) represents a ring-constituting carbon atom, any one of them towhich Rs′ and G does not bind may be replaced with V′,

V′ represents nitrogen atom, or carbon atom substituted with Zx′, Zx′has the same meaning as Zx mentioned above, provided that when Zxcontains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Zx contains amino group, the amino group may be protected withRp²,

Rs′ represents -D-Rx′ or —N(Ry′)(Rz′),

-D-Rx′ and —N(Ry′)(Rz′) have the same meanings as -D-Rx and —N(Ry)(Rz),respectively, provided that when -D-Rx or —N(Ry)(Rz) contains hydroxylgroup, the hydroxyl group may be protected with Rp¹, when -D-Rx or—N(Ry)(Rz) contains amino group, the amino group may be protected withRp²,

G represents chlorine atom, bromine atom, iodine atom, mesylate group,triflate group, or an arenesulfonate group of which aromatic portion maybe substituted with one of T¹ or two or more of the same or differentT¹, and Y′ represents a lower alkyl group having 1 to 4 carbon atoms].

(95) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to the ring-constituting carbon atom C²′ or C³′ inthe aromatic ring (E′).(96) The compound according to (94) or (95) mentioned above, wherein, inthe formula (II), n is an integer of 2.(97) The compound according to any one of (94) to (96) mentioned above,wherein, in the formula (II), Rs′ is —O-Rx′.(98) The compound according to any one of (94) to (97) mentioned above,wherein, in the formula (II), Rs′ is -D-Rx′ or —N(Ry′)(Rz′), D is asingle bind, oxygen atom, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—, Rx′is a linear or branched saturated alkyl group having 3 to 8 carbonatoms, or Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, R¹ is asaturated cyclic alkyl group having 3 to 7 carbon atoms or a condensedsaturated cyclic alkyl group having 6 to 8 carbon atoms, R¹ may besubstituted with one of lower alkyl group having 1 to 4 carbon atoms ortwo or more of the same or different lower alkyl groups having 1 to 4carbon atoms, Q in Rb is phenyl group, thienyl group, furyl group,pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group,thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group,oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolylgroup, naphthyl group, tetrahydronaphthyl group, indanyl group, indenylgroup, quinolyl group, isoquinolyl group, indolyl group, benzofurylgroup, benzothienyl group, benzimidazolyl group, benzoxazolyl group,benzothiazolyl group, indazolyl group, 4H-chromenyl group,dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group,pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group,thienopyrazolyl group, 1,3-dihydrobenzimidazole group,dihydro-3H-benzoxazole group, or dihydro-3H-benzothiazole group, whichbinds to A² at an arbitrary position on the ring, A¹ is a single bind oran alkylene (a) having 1 to 3 carbon atoms, the alkylene (a) may besubstituted with a lower alkyl group having 1 to 4 carbon atoms orphenyl group, A² is a single bind, oxygen atom, sulfur atom, —S(O)—,S(O)₂—, or —N(R⁴)— (provided that when A² is oxygen atom, sulfur atom,—S(O)—, —S(O)₂—, or —N(R⁴)—, A¹ is ethylene or trimethylene), R² and R³independently represent hydrogen atom, a linear or branched saturatedalkyl group having 1 to 4 carbon atoms, oxo group, thioxo group,fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, —OR⁵,—N(R⁶)(R⁶′), —NHCOR⁷, —NHSO₂R⁸, or -A⁶-Qa, or they bind to each other toform methylenedioxy group, Qa may be substituted with one of T¹ or twoor more of the same or different T¹, and is phenyl group, pyridyl group,oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group,imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolylgroup, triazolyl group, tetrazolyl group, naphthyl group, indanyl group,indenyl group, quinolyl group, isoquinolyl group, indolyl group,benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolylgroup, benzothiazolyl group, or indazolyl group, which binds to A⁶ at anarbitrary position on the ring, R⁴ and R⁶ independently representhydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, R⁵ andR⁷ independently represent hydrogen atom or a lower alkyl group having 1to 4 carbon atoms, or -A⁶-Qa, R⁸ represents a lower alkyl group having 1to 4 carbon atoms, R⁶′ has the same meaning as R⁶, or binds to R⁶ toform a 3- to 6-membered ring of a cycloalkyl group or morpholino grouptogether with the nitrogen atom to which they bind, p in Rc is aninteger of 2 to 4, A⁴ is a single bind or methylene or ethylene, A⁵ is—C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, an alkyl group having 1to 8 carbon atoms, or Qa, Re is an alkyl group having 1 to 8 carbonatoms, -A⁶-Qa, —(CH₂)_(i)R¹⁴, —OR²⁸, —SR²⁸, or —N(R²⁹)(R³⁰), i is aninteger of 1 to 3, R¹⁴ is hydroxyl group, an alkoxy group having 1 to 4carbon atoms, carboxyl group, or an N,N-dialkylcarbamoyl group having 1to 4 carbon atoms, R²⁸ is an alkyl group having 1 to 8 carbon atoms or-A⁶-Qa, R²⁹ is an alkyl group having 1 to 8 carbon atoms, analkoxycarbonyl group having 1 to 4 carbon atoms, or -A⁶-Qa, R³⁰represents hydrogen atom or a lower alkyl group having 1 to 4 carbonatoms, or binds to R²⁹ to form a 3- to 6-membered ring ofnitrogen-containing cycloalkyl group or morpholino group together withthe nitrogen atom to which they bind, Rz′ has the same meaning as Rx′,or represents -A⁵-Re, Ry′ represents hydrogen atom, an alkyl grouphaving 1 to 8 carbon atoms, or -A⁶-Qp, or binds to Rz′ to form asaturated or unsaturated nitrogen-containing cyclic substituent having 3to 7 atoms together with the nitrogen atom to which they bind, when-D-Rx′ or —N(Ry′)(Rz′) contains hydroxyl group, the hydroxyl group maybe protected with Rp¹, and when -D-Rx′ or —N(Ry′)(Rz′) contains aminogroup, the amino group may be protected with Rp².(99) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 1 to 3,

G binds to C³′, Rs′ binds to one of the ring-constituting carbon atomsC⁴′, C⁵′, and C⁶′, a ring-constituting carbon atom to which Rs′ does notbind among C⁴′, C⁵′, and C⁶′ may be replaced with V′,

V′ is nitrogen atom or carbon atom substituted with Zx′, Zx′ is fluorineatom, chlorine atom, bromine atom, nitro group, methyl group, hydroxylgroup, methoxy group, amino group, N-methylamino group, N-ethylaminogroup, N-propylamino group, N-isopropylamino group, N,N-dimethylaminogroup, N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylaminogroup, provided that when Zx′ contains hydroxyl group, the hydroxylgroup may be protected with Rp¹, and when Zx′ contains amino group, theamino group may be protected with Rp²,

Rs′ is -D-Rx′ or —N(Ry′)(Rz′), D is oxygen atom or sulfur atom, Rx′ isbutyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group,cyclohexyl group, cycloheptyl group, cyclopentylmethyl group,cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethylgroup, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group,pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group,indanyl group, indolyl group, or dihydrobenzodioxyl group, A² is asingle bind, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)-(provided that when A² is oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ is ethylene), R² and R³ independentlyrepresent hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, dimethylamino group, acetylaminogroup, or methylsulfonylamino group (provided that when Q is phenylgroup, A¹ is a single bind or unsubstituted methylene, and A² is asingle bind, one of R² and R³ is a substituent other than hydrogenatom), p in Rc is an integer of 2 or 3, A⁴ is a single bind ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group or ethyloxycarbonylaminogroup, Rz is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group,or binds to Rz to form pyrrolidino group, piperidino group, piperazinogroup, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, orpyrazol-1-yl group together with the nitrogen atom to which they binds,provided that when -D-Rx′ or —N(Ry′)(Rz′) contains hydroxyl group, thehydroxyl group may be protected with Rp¹, and when -D-Rx′ or—N(Ry′)(Rz′) contains amino group, the amino group may be protected withRp²,

G is chlorine atom, bromine atom, iodine atom, or triflate group, and

Y′ is methyl group or ethyl group.

(100) The compound according to any one of (94) to (96) mentioned above,wherein, in the formula (II), Rs′ is —N(Ry′)(Rz′).(101) The compound according to any one of (94) to (96) mentioned above,wherein, in the formula (II), Rs′ is D-Rx′, and D is sulfur atom,—S(O)—, —S(O)₂— or —C(O)—.(102) The compound according to (94) mentioned above, wherein, in theformula (II), G binds at the position of C²′ in the aromatic ring (E′),Rs′ binds to one of the ring-constituting carbon atoms C³′, C⁴′ and C⁵′,and all of C²′, C³′, C⁴′, C⁵′ and C⁶′ in the aromatic ring (E′) are notreplaced with V′.(103) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 1 to 3,

G binds to C²′, Rs′ binds to one of the ring-constituting carbon atomsC⁴′, C⁵′, and C⁶′, a ring-constituting carbon atom to which Rs′ does notbind among C³′, C⁴′, and C⁵′ may be replaced with V′,

V′ is nitrogen atom, or carbon atom substituted with Zx′, Zx′ isfluorine atom, chlorine atom, bromine atom, nitro group, methyl group,hydroxyl group, methoxy group, amino group, N-methylamino group,N-ethylamino group, N-propylamino group, N-isopropylamino group,N,N-dimethylamino group, N,N-diethylamino group, formylamino group,acetylamino group, carbamoylamino group, mesylamino group, orN,N-dimethylsulfamoylamino group, provided that when Zx′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenZx′ contains amino group, the amino group may be protected with Rp²,

Rs′ is -D-Rx′ or —N(Ry′)(Rz′), D is oxygen atom or sulfur atom, Rx′ isbutyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group,cyclohexyl group, cycloheptyl group, cyclopentylmethyl group,cyclohexylmethyl group, 2-cyclopentylethyl group, 2-cyclohexylethylgroup, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group,pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group,indanyl group, indolyl group, or dihydrobenzodioxyl group, A² is asingle bind, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)-(provided that when A² is oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ is ethylene), R² and R³ independentlyrepresent hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, dimethylamino group, acetylaminogroup, or methylsulfonylamino group (provided that when Q is phenylgroup, A¹ is a single bind or unsubstituted methylene, and A² is asingle bind, one of R² and R³ is a substituent other than hydrogenatom), p in Rc is an integer of 2 or 3, A⁴ is a single bind ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylaminogroup, Rz is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry is hydrogen atom, methyl group, ethyl group or isobutyl group,or binds to Rz to form pyrrolidino group, piperidino group, piperazinogroup, morpholino group, pyrrol-1-yl group, imidazol-1-yl group, orpyrazol-1-yl group together with the nitrogen atom, provided that when-D-Rx′ or —N(Ry′)(Rz′) contains hydroxyl group, the hydroxyl group maybe protected with Rp¹, and when -D-Rx′ or —N(Ry′)(Rz′) contains aminogroup, the amino group may be protected with Rp²,

G is chlorine atom, bromine atom, iodine atom, or triflate group, and

Y′ is methyl group or ethyl group.

(104) The compound according to (102) or (103) mentioned above, wherein,in the formula (II), n is an integer of 2, Rs′ binds to C³′ in thearomatic ring (E′), Rs′ is —O-Rx′, and Y′ is methyl group or ethylgroup.(105) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C²′ is a ring-constituting carbon atom to which G binds, C³′ is aring-constituting carbon atom to which Rs′ binds, C⁴′ may be replacedwith V′, C⁵′ and C⁶′ are unsubstituted ring-constituting carbon atoms,

V′ is nitrogen atom, or carbon atom substituted with Zx′, Zx′ isfluorine atom, methyl group, hydroxyl group, amino group, N-methylaminogroup, or N,N-dimethylamino group, provided that when Zx′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenZx′ contains amino group, the amino group may be protected with Rp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(106) The compound according to (102) or (103) mentioned above, wherein,in the formula (II), n is an integer of 2, Rs′ binds at the position ofC⁴′ in the aromatic ring (E′), Rs′ is —O-Rx′, and Y is methyl group orethyl group.(107) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C²′ is a ring-constituting carbon atom to which G binds, C⁴′ is aring-constituting carbon atom to which Rs′ binds, C⁵′ may be replacedwith V′, C³′ and C⁶′ are unsubstituted ring-constituting carbon atoms,

V′ is nitrogen atom, or carbon atom substituted with Zx′, Zx′ isfluorine atom, methyl group, hydroxyl group, amino group, N-methylaminogroup, or N,N-dimethylamino group, provided that when Zx′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenZx′ contains amino group, the amino group may be protected with Rp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(108) The compound according to (102) or (103) mentioned above, wherein,in the formula (II), n is an integer of 2, Rs′ binds at the position ofC⁵′ in the aromatic ring (E′), Rs′ is —O-Rx′, and Y′ is methyl group orethyl group.(109) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to C³′ in the aromatic ring (E′), Rs′ binds to C⁵′or C⁶′ in the aromatic ring (E′), and all of C²′, C³′, C⁴′, C⁵′ and C⁶′in the aromatic ring (E′) are not replaced with V′.(110) The compound according to (109) mentioned above, wherein, in theformula (II), n is an integer of 2, Rs′ binds to C⁵′ in the aromaticring (E′), and Rs′ is —O-Rx′.(111) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C³′ is carbon atom to which G binds, C⁵′ is carbon atom to which Rs′binds, C²′, C⁴′, and C⁶′ are unsubstituted ring-constituting carbonatoms,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group or 2-(N-ethyl-N-phenylamino)ethylgroup,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(112) The compound according to (109) mentioned above, wherein, in theformula (II), n is an integer of 2, Rs′ binds to C⁶′ in the aromaticring (E′), and Rs′ is —O-Rx′.(113) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to C³′ in the aromatic ring (E′), Rs′ binds to C⁴′in the aromatic ring (E′), and C⁶′ is V′.(114) The compound according to (113) mentioned above, wherein, in theformula (II), n is an integer of 2, V′ is carbon atom substituted withZx′, and Rs′ is —O-Rx′.(115) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C³′ is carbon atom to which G binds, C⁴′ is a carbon atom to which Rs′binds, C⁶′ is carbon atom substituted with Zx′, C²′ and C⁵′ areunsubstituted ring-constituting carbon atoms,

Zx′ is fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Zx′ contains amino group, the amino group may be protected withRp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(116) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to C³′ in the aromatic ring (E′), Rs′ binds to C⁴′in the aromatic ring (E′), C⁵′ is nitrogen atom, and C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms.(117) The compound according to (116) mentioned above, wherein, in theformula (II), n is an integer of 2, and Rs′ is —O-Rx′.(118) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C³′ is carbon atom to which G binds, C⁴′ is carbon atom to which Rs′binds, C⁵′ is nitrogen atom, C²′ and C⁶′ are unsubstitutedring-constituting carbon atoms,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(119) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to C³′ in the aromatic ring (E′), Rs′ binds to C⁴′in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, and D is a single bind, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—.(120) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C³′ is carbon atom to which G binds, C⁴′ is a carbon atom to which Rs′binds, C⁵′ is a ring-constituting carbon atom substituted with Zx′, oran unsubstituted ring-constituting carbon atom, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms,

Zx′ is fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Zx′ contains amino group, the amino group may be protected withRp²,

Rs′ is —S-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(121) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to C³′ in the aromatic ring (E′), Rs′ binds to C⁴′in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, and Rs′ is—N(Ry′)(Rz′).(122) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C³′ is carbon atom to which G binds, C⁴′ is a carbon atom to which Rs′binds, C⁵′ is a ring-constituting carbon atom substituted with Zx′, oran unsubstituted ring-constituting carbon atom, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms,

Zx′ is fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Zx′ contains amino group, the amino group may be protected withRp²,

Rs′ is —N(Ry′)(Rz′), Rz′ is butyl group, isobutyl group, 2-ethylbutylgroup, cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry′ is hydrogen atom, methyl group, ethyl group or isobutylgroup, or binds to Rz′ to form pyrrolidino group, piperidino group, ormorpholino group together with nitrogen atom to which they binds,provided that when —N(Ry′)(Rz′) contains hydroxyl group, the hydroxylgroup may be protected with Rp¹, and when —N(Ry′)(Rz′) contains aminogroup, the amino group may be protected with Rp²,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(123) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2, G binds to C³′ in the aromatic ring(E′), Rs′ binds to C⁴′ in the aromatic ring (E′), C⁵′ is carbon atomsubstituted with —N(Rn¹)(Rn²) group (provided that one of Rn¹ and Rn² isa substituent other than hydrogen atom), C²′ and C⁶′ are unsubstitutedring-constituting carbon atoms, and Rs′ is —O-Rx′.(124) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C³′ is carbon atom to which G binds, C⁴′ is carbon atom to which Rs′binds, C⁵′ is carbon atom substituted with Zx′, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms,

Zx′ is N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, or N,N-dimethylsulfamoylamino group, provided that when Zx′contains amino group, the amino group may be protected with Rp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(125) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to C³′ in the aromatic ring (E′), Rs′ binds to C⁴′in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, and Rx′ has the same meaning as Rc, provided that when Rccontains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Rc contains amino group, the amino group may be protected withRp².(126) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2,

C³′ is carbon atom to which G binds, C⁴′ is a carbon atom to which Rs′binds, C⁵′ is a ring-constituting carbon atom substituted with Zx′, oran unsubstituted ring-constituting carbon atom, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms,

Zx′ is fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Zx′ contains amino group, the amino group may be protected withRp²,

Rs′ is —O-Rx′, Rx′ has the same meaning as Rc, provided that when Rccontains hydroxyl group, the hydroxyl group may be protected with Rp¹, pin Rc is an integer of 2, A⁴ is a single bind or methylene, A⁵ is—C(O)—, —C(S)—, or —S(O)₂—, Rd is methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, cyclopropyl group,cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, or 4-fluorophenylmethyl group, Re isisopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, propyloxy group,isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group,cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group,cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group,4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxygroup, N-propylamino group, N-isopropylamino group, N-butylamino group,N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group,N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, pyrrolidino group, piperidino group, ormorpholino group,

G is bromine atom or iodine atom, and

Y′ is methyl group or ethyl group.

(127) The compound according to (94) mentioned above, wherein, in theformula (II), G binds to C³′ in the aromatic ring (E′), Rs′ binds to C⁴′in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is—O-Rx′, and Rx′ is a linear or branched saturated alkyl group having 3to 8 carbon atoms, or Ra or Rb.(128) The compound according to (94) mentioned above, wherein, in theformula (II), n is an integer of 2, G binds to C³′ in the aromatic ring(E′), Rs′ binds to C⁴′ in the aromatic ring (E′), C⁵′ is carbon atomsubstituted with nitro group, C²′ and C⁶′ are unsubstitutedring-constituting carbon atoms, and Rs′ is —O-Rx′.(129) A compound represented by the following formula (III):

[In the formula, C²′, C³′, C⁴′, C⁵′ and C⁶′ in the aromatic ring (E′)represent a ring-constituting carbon atom, any one of these atoms towhich Rs′ and AR′ does not bind may be replaced with V′, and AR′ has thesame meaning as that of AR, provided that when AR contains hydroxylgroup, the hydroxyl group may be protected with Rp¹, and when ARcontains amino group, the amino group may be protected with Rp².].(130) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to the atom of C²′ or C³′ in the aromatic ring(E′).(131) The compound according to (129) or (130) mentioned above, wherein,in the formula (III), AR′ is a residue of naphthalene, benzofuran,benzo[b]thiophene, indole, benzothiazole, dihydro-3H-benzothiazole,quinoline, dihydro-1H-quinoline, benzo[d]isothiazole, 1H-indazole,benzo[c]isothiazole, 2H-indazole, imidazo[1,2-a]pyridine,1H-pyrrolo[2,3-b]pyridine, isoquinoline, dihydro-2H-isoquinoline,cinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole,1H-pyrrolo[3,2-b]pyridine, benzo[1,2,5]thiadiazole, 1H-benzotriazole,1,3-dihydropyrrolo[2,3-b]pyridine, 1,3-dihydrobenzimidazole,dihydro-3H-benzoxazole, phthalazine, [1,8]naphthalidine,[1,5]naphthalidine, 1H-pyrrolo[3,2-c]pyridine,1H-pyrrolo[2,3-c]pyridine, 1H-pyrazolo[4,3-b]pyridine,1H-pyrazolo[4,3-c]pyridine, 1H-pyrazolo[3,4-c]pyridine,1H-pyrazolo[3,4-b]pyridine, [1,2,4]triazolo[4,3-a]pyridine,thieno[3,2-c]pyridine, thieno[3,2-b]pyridine, 1H-thieno[3,2-c]pyrazole,benzo[d]isoxazole, benzo[c]isoxazole, indolizine, 1,3-dihydroindole,1H-pyrazolo[3,4-d]thiazole, 2H-isoindole,[1,2,4]triazolo[1,6-a]pyrimidine, 1H-pyrazolo[3,4-b]pyrazine,1H-imidazo[4,5-b]pyrazine, 7H-purine, or 4H-chromene (the aforementionedresidue may be substituted with one of Xa or two or more of the same ordifferent Xa, when AR′ contains hydroxyl group, the hydroxyl group maybe protected with Rp¹, and when AR′ contains amino group, the aminogroup may be protected with Rp²).(132) The compound according to (129) or (130) mentioned above, wherein,in the formula (III), AR′ is naphthalen-2-yl group, naphthalen-1-ylgroup, benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-ylgroup, benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa, when AR′ contains hydroxylgroup, the hydroxyl group may be protected with Rp¹, and when AR′contains amino group, the amino group may be protected with Rp²).(133) The compound according to (129) or (130) mentioned above, wherein,in the formula (III), AR′ is a residue of naphthalene, benzofuran,benzo[b]thiophene, indole, benzothiazole, dihydro-3H-benzothiazole,quinoline, dihydro-1H-quinoline, benzo[d]isothiazole, 1H-indazole,benzo[c]isothiazole, 2H-indazole, imidazo[1,2-a]pyridine,1H-pyrrolo[2,3-b]pyridine, isoquinoline, or dihydro-2H-isoquinoline (theaforementioned residue may be substituted with one of Xa or two or moreof the same or different Xa, when AR′ contains hydroxyl group, thehydroxyl group may be protected with Rp¹, and when AR′ contains aminogroup, the amino group may be protected with Rp²).(134) The compound according to (129) or (130) mentioned above, wherein,in the formula (III), AR′ is a residue of cinnoline, quinazoline,quinoxaline, 1H-benzimidazole, benzoxazole, 1H-pyrrolo[3,2-b]pyridine,benzo[1,2,5]thiadiazole, 1H-benzotriazole,1,3-dihydropyrrolo[2,3-b]pyridine, 1,3-dihydrobenzimidazole,dihydro-3H-benzoxazole, phthalazine, [1,8]naphthalidine,[1,5]naphthalidine, 1H-pyrrolo[3,2-c]pyridine,1H-pyrrolo[2,3-c]pyridine, 1H-pyrazolo[4,3-b]pyridine,1H-pyrazolo[4,3-c]pyridine, 1H-pyrazolo[3,4-c]pyridine,1H-pyrazolo[3,4-b]pyridine, [1,2,4]triazolo[4,3-a]pyridine,thieno[3,2-c]pyridine, thieno[3,2-b]pyridine, 1H-thieno[3,2-c]pyrazole,benzo[d]isoxazole, benzo[c]isoxazole, indolizine, 1,3-dihydroindole,1H-pyrazolo[3,4-d]thiazole, 2H-isoindole,[1,2,4]triazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyrazine,1H-imidazo[4,5-b]pyrazine, 7H-purine, or 4H-chromene (the aforementionedresidue may be substituted with one of Xa or two or more of the same ordifferent Xa, when AR′ contains hydroxyl group, the hydroxyl group maybe protected with Rp¹, and when AR′ contains amino group, the aminogroup may be protected with Rp²).(135) The compound according to any one of (129) to (134) mentionedabove, wherein, in the formula (III), Rs′ is —O-Rx′.(136) The compound according to any one of (129) to (135) mentionedabove, wherein, in the formula (III), Rs′ is -D-Rx′ or —N(Ry′)(Rz′), Dis a single bind, oxygen atom, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—,Rx′ is a linear or branched saturated alkyl group having 3 to 8 carbonatoms, or Ra, Rb, or Rc, k in Ra is 0 or an integer of 1 to 3, R¹ is asaturated cyclic alkyl group having 3 to 7 carbon atoms or a condensedsaturated cyclic alkyl group having 6 to 8 carbon atoms, R¹ may besubstituted with one of lower alkyl group having 1 to 4 carbon atoms ortwo or more of the same or different lower alkyl groups having 1 to 4carbon atoms, Q in Rb is phenyl group, thienyl group, furyl group,pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group,thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group,oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolylgroup, naphthyl group, tetrahydronaphthyl group, indanyl group, indenylgroup, quinolyl group, isoquinolyl group, indolyl group, benzofurylgroup, benzothienyl group, benzimidazolyl group, benzoxazolyl group,benzothiazolyl group, indazolyl group, 4H-chromenyl group,dihydrobenzodioxyl group, benzoisoxazolyl group, pyrrolopyridinyl group,pyrazolopyridinyl group, triazolopyridinyl group, thienopyridinyl group,thienopyrazolyl group, 1,3-dihydrobenzimidazole group,dihydro-3H-benzoxazole group, or dihydro-3H-benzothiazole group, whichbinds to A² at an arbitrary position on the ring, A¹ is a single bind oran alkylene (a) having 1 to 3 carbon atoms, the alkylene (a) may besubstituted with a lower alkyl group having 1 to 4 carbon atoms orphenyl group may be substituted with, A² is a single bind, oxygen atom,sulfur atom, —S(O)—, —S(O)₂—, or —N(R⁴)— (provided that when A² isoxygen atom, sulfur atom,—S(O)—, —S(O)₂—, or —N(R⁴)—, A¹ is ethylene or trimethylene), R² and R³independently represent hydrogen atom, a linear or branched saturatedalkyl group having 1 to 4 carbon atoms, oxo group, thioxo group,fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, —OR⁵,—N(R⁶)(R⁶′), —NHCOR⁷, —NHSO₂R⁸, or -A⁶-Qa, or they binds to each otherto form methylenedioxy group, Qa is phenyl group, pyridyl group,oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group,imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolylgroup, triazolyl group, tetrazolyl group, naphthyl group, indanyl group,indenyl group, quinolyl group, isoquinolyl group, indolyl group,benzofuryl group, benzothienyl group, benzimidazolyl group, benzoxazolylgroup, benzothiazolyl group, or indazolyl group, which may besubstituted with one of T¹ or two or more of the same or different T¹,and binds to A⁶ at an arbitrary position on the ring, R⁴ and R⁶independently represent hydrogen atom or a lower alkyl group having 1 to4 carbon atoms, R⁵ and R⁷ independently represent hydrogen atom, a loweralkyl group having 1 to 4 carbon atoms, or -A⁶-Qa, R⁸ is a lower alkylgroup having 1 to 4 carbon atoms, R⁶′ has the same meaning as R⁶, orbinds to R⁶ to form a 3- to 6-membered ring together with the nitrogenatom to which they bind to form a saturated nitrogen-containing alkylgroup or morpholino group, p in Rc is an integer of 2 to 4, A⁴ is asingle bind or methylene or ethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—,Rd is hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or Qa,Re is an alkyl group having 1 to 8 carbon atoms, -A⁶-Qa, —(CH₂)_(i)R¹⁴,—OR²⁸, —SR²⁸, or —N(R²⁹)(R³⁰), i is an integer of 1 to 3, R¹⁴ ishydroxyl group, an alkoxy group having 1 to 4 carbon atoms, carboxylgroup, or an N,N-dialkylcarbamoyl group having 1 to 4 carbon atoms, R²⁸is an alkyl group having 1 to 8 carbon atoms or -A⁶-Qa, R²⁹ is an alkylgroup having 1 to 8 carbon atoms, an alkoxycarbonyl group having 1 to 4carbon atoms, or -A⁶-Qa, R³⁰ is hydrogen atom or a lower alkyl grouphaving 1 to 4 carbon atoms, or binds to R²⁹ to form a 3- to 6-memberedring together with the nitrogen atom to which they bind to form asaturated nitrogen-containing alkyl group or morpholino group, Rz′ hasthe same meaning as Rx′, or represents -A⁵-Re, Ry′ is hydrogen atom, analkyl group having 1 to 8 carbon atoms, or -A⁶-Qp, or binds to Rz′ toform a saturated or unsaturated nitrogen-containing cyclic substituenthaving 3 to 7 atoms, when -D-Rx′ or —N(Ry′)(Rz′) contains hydroxylgroup, the hydroxyl group may be protected with Rp¹, and when -D-Rx′ or—N(Ry′)(Rz′) contains amino group, the amino group may be protected withRp².(137) The compound according to any one of (129) to (136) mentionedabove, wherein, in the formula (III), Rs′ is —N(Ry′)(Rz′).(138) The compound according to any one of (129) to (136) mentionedabove, wherein, in the formula (III), Rs′ is -D-Rx′, D is sulfur atom,—S(O)—, —S(O)₂—, or —C(O)—.(139) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds at the position of C²′ in the aromatic ring(E′), and Rs′ binds to one of the ring-constituting carbon atoms C³′,C⁴′, and C^(5′.)(140) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C²′, Rs′ binds to any one of the atoms C³′,C⁴′, and C⁵′, a ring-constituting carbon atom to which Rs′ does not bindamong C³′, C⁴′, and C⁵′ may be replaced with V′,

V′ is nitrogen atom, or carbon atom substituted with Zx′, Zx′ is onekind of group selected from the group consisting of fluorine atom,chlorine atom, bromine atom, nitro group, methyl group, hydroxyl group,methoxy group, amino group, N-methylamino group, N-ethylamino group,N-propylamino group, N-isopropylamino group, N,N-dimethylamino group,N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, and N,N-dimethylsulfamoylaminogroup, provided that when Zx′ contains hydroxyl group, the hydroxylgroup may be protected with Rp¹, and when Zx′ contains amino group, theamino group may be protected with Rp²,

Rs′ is -D-Rx′ or —N(Ry′)(Rz′), D is oxygen atom or sulfur atom, Rx′ isbutyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group,cyclohexyl group, cycloheptyl group, cyclopentylmethyl group,cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethylgroup, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group,pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group,indanyl group, indolyl group, or dihydrobenzodioxyl group, A² is asingle bind, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)-(provided that when A² is oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ is ethylene), R² and R³ independentlyrepresent hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, dimethylamino group, acetylaminogroup, or methylsulfonylamino group (provided that when Q is phenylgroup, A¹ is a single bind or unsubstituted methylene, and A² is asingle bind, one of R² and R³ is a substituent other than hydrogenatom), p in Rc is an integer of 2 or 3, A⁴ is a single bind ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, or ethyloxycarbonylaminogroup, Rz′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry′ is hydrogen atom, methyl group, ethyl group or isobutylgroup, or binds to Rz′ to form pyrrolidino group, piperidino group,piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-ylgroup or pyrazol-1-yl group together with the nitrogen atom, providedthat when -D-Rx′ or —N(Ry′)(Rz′) contains hydroxyl group, the hydroxylgroup may be protected with Rp¹, and when -D-Rx′ or —N(Ry′)(Rz′)contains amino group, the amino group may be protected with Rp²,

AR′ is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-yl,group, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), and Xa is oxo group, thioxogroup, fluorine atom, chlorine atom, trifluoromethyl group, methylgroup, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethylgroup, 2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxylgroup, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, provided that when AR′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenAR′ contains amino group, the amino group may be protected with Rp².

(141) The compound according to (139) or (140) mentioned above, wherein,in the formula (III), Rs′ is —O-Rx′, and all of C²′, C³′, C⁴′, C⁵′ andC⁶′ in the aromatic ring (E′) are not replaced with V′.(142) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds at the position of C²′ in the aromatic ring(E′), Rs′ binds to one of the ring-constituting carbon atoms C³′, C⁴′,and C⁵′, Rs′ is —O-Rx′, and all of C²′, C³′, C⁴′, C⁵′ and C⁶′ in thearomatic ring (E′) are not replaced with V.(143) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds at the position of C²′ in the aromatic ring(E′), Rs′ binds to one of the ring-constituting carbon atoms C³′, C⁴′,and C⁵′, Rs′ is —O-Rx′, and all of C²′, C³′, C⁴′, C⁵′ and C⁶′ in thearomatic ring (E′) are not replaced with V.(144) The compound according to any one of (139) to (143) mentionedabove, wherein, in the formula (III), Rs′ binds to C^(3′.)(145) The compound according to (129) mentioned above, wherein, in theformula (III), C²′ is carbon atom to which AR′ binds, C³′ is carbon atomto which Rs′ binds, C⁴′ may be replaced with V′, C⁵′ and C⁶′ areunsubstituted ring-constituting carbon atoms,

V′ is nitrogen atom, or carbon atom substituted with Zx′, Zx′ isfluorine atom, methyl group, hydroxyl group, amino group, N-methylaminogroup, or N,N-dimethylamino group, provided that when Zx′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenZx′ contains amino group, the amino group may be protected with Rp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup, and

AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group (the aforementioned groups may be substituted withone of Xa or two or more of the same or different Xa), provided thatwhen AR′ contains hydroxyl group, the hydroxyl group may be protectedwith Rp¹, and when AR′ contains amino group, the amino group may beprotected with Rp².

(146) The compound according to (139) to (143) mentioned above, wherein,in the formula (III), Rs′ binds to C^(4′.)(147) The compound according to (129) mentioned above, wherein, in theformula (III), C²′ is carbon atom to which AR′ binds, C⁴′ is carbon atomto which Rs′ binds, C⁵′ may be replaced with V′, C³′ and C⁶′ areunsubstituted ring-constituting carbon atoms,

V′ is nitrogen atom, or carbon atom substituted with Zx′, Zx′ isfluorine atom, methyl group, hydroxyl group, amino group, N-methylaminogroup, or N,N-dimethylamino group, provided that when Zx′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenZx′ contains amino group, the amino group may be protected with Rp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup, and

AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when AR′ containsamino group, the amino group may be protected with Rp².

(148) The compound according to any one of (139) to (143) mentionedabove, wherein, in the formula (III), Rs′ binds to C⁵′.(149) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds tothe atom C⁵′ or C⁶′ in the aromatic ring (E′).(150) The compound according to (149) mentioned above, wherein, in theformula (III), Rs′ is —O-Rx′, and all of C²′, C³′, C⁴′, C⁵′ and C⁶′ inthe aromatic ring (E′) are not replaced with V.(151) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds tothe atom C⁵′ or C⁶′ in the aromatic ring (E′), Rs′ is —O-Rx′, and all ofC²′, C³′, C⁴′, C⁵′ and C⁶′ in the aromatic ring (E′) are not replacedwith V.(152) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds tothe atom C⁵′ or C⁶′ in the aromatic ring (E′), Rs′ is —O-Rx′, and all ofC²′, C³′, C⁴′, C⁵′ and C⁶′ in the aromatic ring (E′) are not replacedwith V.(153) The compound according to any one of (149) to (152) mentionedabove, wherein, in the formula (III), Rs′ binds to C^(5′.)(154) The compound according to (129) mentioned above, wherein, in theformula (III), C³′ is carbon atom to which AR′ binds, C⁵′ is carbon atomto which Rs′ binds, C²′, C⁴′, and C⁶′ are unsubstitutedring-constituting carbon atoms,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup, and

AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when AR′ containsamino group, the amino group may be protected with Rp².

(155) The compound according to any one of (149) to (152) mentionedabove, wherein, in the formula (III), Rs′ binds to C^(6′.)(156) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), and C⁶′ is V′.(157) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁶′ is carbon atom substituted with Zx,C²′ and C⁵′ are unsubstituted carbon atoms, and Rs′ is —O-Rx′.(158) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁶′ is carbon atom substituted with Zx,C²′ and C⁵′ are unsubstituted ring-constituting carbon atoms, and Rs′ is—O-Rx′.(159) The compound according to (129) mentioned above, wherein, in theformula (III), C³′ is carbon atom to which AR′ binds, C⁴′ is a carbonatom to which Rs′ binds, C⁶′ is carbon atom substituted with Zx′, C²′and C⁵′ are unsubstituted ring-constituting carbon atoms,

Zx′ is fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Zx′ contains amino group, the amino group may be protected withRp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup, and

AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, provided that when Ar′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when AR′ containsamino group, the amino group may be protected with Rp².

(160) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is nitrogen atom, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms, and Rs′ is —O-Rx′.(161) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is nitrogen atom, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms, and Rs′ is —O-Rx′.(162) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is nitrogen atom, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms, and Rs′ is —O-Rx′.(163) The compound according to (129) mentioned above, wherein, in theformula (III), C³′ is carbon atom to which AR′ binds, C⁴′ is carbon atomto which Rs′ binds, C⁵′ is nitrogen atom, C²′ and C⁶′ are unsubstitutedring-constituting carbon atoms,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup, and

AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when AR′ containsamino group, the amino group may be protected with Rp².

(164) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, D is a single bind, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—.(165) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, and D is a single bind, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—.(166) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, and D is a single bind, sulfur atom, —S(O)—, —S(O)₂—, or —C(O)—.(167) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, and Rs′ is—N(Ry′)(Rz′).(168) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, and Rs′ is—N(Ry′)(Rz′).(169) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, and Rs′ is—N(Ry′)(Rz′).(170) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵ is carbon atom substituted with—N(Rn¹)(Rn²) (provided that one of Rn¹ and Rn² is a substituent otherthan hydrogen atom), C²′ and C⁶′ are unsubstituted ring-constitutingcarbon atoms, and Rs′ is —O-Rx′.(171) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is carbon atom substituted with—N(Rn¹)(Rn²) (provided that one of Rn¹ and Rn² is a substituent otherthan hydrogen atom), C²′ and C⁶′ are unsubstituted ring-constitutingcarbon atoms, and Rs′ is —O-Rx′.(172) The compound according to (123) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is carbon atom substituted with—N(Rn¹)(Rn²) (provided that one of Rn¹ and Rn² is a substituent otherthan hydrogen atom), C²′ and C⁶′ are unsubstituted ring-constitutingcarbon atoms, and Rs′ is —O-Rx′.(173) The compound according to (129) mentioned above, wherein, in theformula (III), C³′ is carbon atom to which AR′ binds, C⁴′ is carbon atomto which Rs′ binds, C⁵′ is carbon atom substituted with Zx′, C²′ and C⁶′are unsubstituted ring-constituting carbon atoms,

Zx′ is N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, or N,N-dimethylsulfamoylamino group, provided that when Zx′contains amino group, the amino group may be protected with Rp²,

Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup, and

AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when AR′ containsamino group, the amino group may be protected with Rp².

(174) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, and Rx′ has the same meaning as Rc, provided that when Rccontains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Rc contains amino group, the amino group may be protected withRp².(175) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, and Rx′ has the same meaning as Rc, provided that when Recontains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Re contains amino group, the amino group may be protected withRp².(176) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, Rs′ is-D-Rx′, and Rx′ has the same meaning as Re, provided that when Recontains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Re contains amino group, the amino group may be protected withRp².(177) The compound according to (129) mentioned above, wherein, in theformula (III), C³′ is carbon atom to which AR′ binds, C⁴′ is a carbonatom to which Rs′ binds, C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms,

Zx′ is fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when Zx′ contains amino group, the amino group may be protected withRp²,

Rs′ is —O-Rx′, Rx′ has the same meaning as Re, provided that when Recontains hydroxyl group, the hydroxyl group may be protected with Rp¹, pin Re is an integer of 2, A⁴ is a single bind or methylene, A⁵ is—C(O)—, —C(S)—, or —S(O)₂—, Rd is methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, cyclopropyl group,cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, or 4-fluorophenylmethyl group, Re isisopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, propyloxy group,isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group,cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group,cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group,4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxygroup, N-propylamino group, N-isopropylamino group, N-butylamino group,N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group,N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, pyrrolidino group, piperidino group, ormorpholino group, and

AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group, 6(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when AR′ containsamino group, the amino group may be protected with Rp².

(178) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′, Rs′ binds to any one of the atoms C⁴′,C⁵′, and C⁶′, a ring-constituting carbon atom to which Rs′ does not bindamong C⁴′, C⁵′, and C⁶′ may be replaced with V′,

V′ is nitrogen atom, or carbon atom substituted with Zx′, Zx′ isfluorine atom, chlorine atom, bromine atom, nitro group, methyl group,hydroxyl group, methoxy group, amino group, N-methylamino group,N-ethylamino group, N-propylamino group, N-isopropylamino group,N,N-dimethylamino group, N,N-diethylamino group, formylamino group,acetylamino group, carbamoylamino group, mesylamino group, orN,N-dimethylsulfamoylamino group, provided that when Zx′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenZx′ contains amino group, the amino group may be protected with Rp²,

Rs′ is -D-Rx′ or —N(Ry′)(Rz′), D is oxygen atom or sulfur atom, Rx′ isbutyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group,cyclohexyl group, cycloheptyl group, cyclopentylmethyl group,cyclohexylmethyl group, 2-cyclopentylethyl group, or 2-cyclohexylethylgroup, or Rb or Rc, Q in Rb is phenyl group, thienyl group, furyl group,pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group,indanyl group, indolyl group, or dihydrobenzodioxyl group, A² is asingle bind, oxygen atom, sulfur atom., —N(methyl)-, or—N(ethyl)-(provided that when A² is oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ is ethylene), R² and R³ independentlyrepresent hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, dimethylamino group, acetylaminogroup, or methylsulfonylamino group (provided that when Q is phenylgroup, A¹ is a single bind or unsubstituted methylene, and A² is asingle bind, one of R² and R³ is a substituent other than hydrogenatom), p in Rc is an integer of 2 or 3, A⁴ is a single bind ormethylene, A⁵ is —C(O)—, —C(S)—, or —S(O)₂—, Rd is hydrogen atom, ormethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, cyclopropyl group, cyclopropylmethyl group, cyclopentylgroup, cyclopentylmethyl group, cyclohexyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, benzyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group, orpyridin-4-yl group, Re is methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group or ethyloxycarbonylaminogroup, Rz′ is butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, or (morpholino-4-yl)carbonylgroup, Ry′ is hydrogen atom, methyl group, ethyl group or isobutylgroup, or binds to Rz′ to form pyrrolidino group, piperidino group,piperazino group, morpholino group, pyrrol-1-yl group, imidazol-1-ylgroup, or pyrazol-1-yl group together with the nitrogen atom, providedthat when -D-Rx′ or —N(Ry′)(Rz′) contains hydroxyl group, the hydroxylgroup may be protected with Rp¹, and when the substituent -D-Rx′ or—N(Ry′)(Rz′) contains amino group, the amino group may be protected withRp²,

AR′ is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), and Xa is oxo group, thioxogroup, fluorine atom, chlorine atom, trifluoromethyl group, methylgroup, ethyl group, propyl group, 2-hydroxyethyl group, carboxymethylgroup, 2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxylgroup, methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, provided that when AR′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whenAR′ contains amino group, the amino group may be protected with Rp².

(179) The compound according to (119) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, and Rs′ is—O-Rx′.(180) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, and D isoxygen atom.(181) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is a ring-constituting carbon atomsubstituted with Zx′, or an unsubstituted ring-constituting carbon atom,C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, and Rs′ is—O-Rx′.(182) The compound according to (129) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is carbon atom substituted with nitrogroup, C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, andRs′ is —O-Rx′.(183) The compound according to (131) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is carbon atom substituted with nitrogroup, C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, andRs′ is —O-Rx′.(184) The compound according to (132) mentioned above, wherein, in theformula (III), AR′ binds to C³′ in the aromatic ring (E′), Rs′ binds toC⁴′ in the aromatic ring (E′), C⁵′ is carbon atom substituted with nitrogroup, C²′ and C⁶′ are unsubstituted ring-constituting carbon atoms, andRs′ is —O-Rx′.(185) An agent for prophylactic and/or therapeutic treatment offibrosis, which contains a type 4 PLA₂ inhibitor as an activeingredient.(186) An agent for prophylactic and/or therapeutic treatment ofpulmonary fibrosis, which contains a type 4 PLA₂ inhibitor as an activeingredient.(187) The prophylactic and/or therapeutic agent according to (186),wherein the pulmonary fibrosis is drug-induced pulmonary fibrosis.(188) The prophylactic and/or therapeutic agent according to (187),wherein the drug-induced pulmonary fibrosis is a disease induced by oneor more kinds of medicaments among methotrexate, sodium aurothiomalate,auranofin, D-penicillamine, bucillamine, actarit, salazosulfapyridine,cyclophosphamide, Taxol, etoposide, cisplatin, vincristine, vinblastine,irinotecan, gefitinib, and bleomycin.(189) The prophylactic and/or therapeutic agent according to (187),wherein the drug-induced pulmonary fibrosis is a disease induced by oneor more kinds of medicaments among methotrexate and bleomycin.(190) The prophylactic and/or therapeutic agent according to (186),wherein the type 4 PLA₂ inhibitor is a compound represented by theformula (I) or a pharmacologically acceptable salt thereof.(191) The prophylactic and/or therapeutic agent according to (186),wherein the type 4 PLA₂ inhibitor is an inhibitor selected from thegroup consisting of4-(1-benzhydryl-6-chloro-1H-indol-3-ylmethyl)-3-methoxybenzoic acid,4-{4-[2-(2-[bis(4-chlorophenyl)methoxy]ethylsulfonyl)ethoxy]phenyl}-1,1,1-trifluoro-2-butanone,N-{1-[2-(2,4-difluorobenzoyl)benzoyl]-4-tritylsulfanylpyrrolidin-2-ylmethyl}-4-(2,4-dioxothiazolidin-5-ylidenemethyl)benzoicacid amide,4-methyl-2-oxo-5-(5,6,7,8-tetrahydronaphthalen-2-yl)oxazolidine-3-carbonxylicacid (6-methoxytetrahydropyran-2-yl)amide,4-methyl-2-oxo-5-(4-methylphenyl)thiazolidine-3-carbonxylic acid(tetrahydropyran-2-yl)amide,4-[3-(4-decyloxyphenyloxy)-2-oxopropyloxy]benzoic acid, and1-{2-[4-(carboxymethyl)phenoxy]ethyl}-3-dodecanoylindole-2-carbonxylicacid.

The compound (I) of the present invention or a pharmaceuticallyacceptable salt thereof has an action of suppressing the production ofboth of prostaglandins and leukotrienes, and said compound hascharacteristic features that, when administered to a human or animal,the compound exerts superior prophylactic and/or therapeutic effect ondiseases or pathological conditions in which a prostaglandin and/orleukotriene is involved, and the compound has extremely low toxicity.The compounds (II) and (III) of the present invention are syntheticintermediates useful for the production of the compound (I) of thepresent invention. Furthermore, it was confirmed that a type 4 PLA₂inhibitor is useful as a prophylactic and/or therapeutic agent forfibrosis, in particular, pulmonary fibrosis, especially drug-inducedpulmonary fibrosis, which was induced as a side effect of a medicament.

BEST MODE FOR CARRYING OUT THE INVENTION

In the present specification, carbon atom may sometimes be representedsimply by “C”, hydrogen atom by “H”, oxygen atom by “O”, sulfur atom by“S”, and nitrogen atom by “N”.

Examples of Link in the aforementioned general formula (I) include asaturated straight hydrocarbon chain having 1 to 3 carbon atoms or anunsaturated straight hydrocarbon chain having 2 or 3 carbon atoms. Inthe present invention, the straight chain of the saturated straighthydrocarbon chain is preferably unsubstituted. The straight chain of theunsaturated straight hydrocarbon chain is also preferably unsubstituted.As the saturated straight hydrocarbon chain, —(CH₂)_(n)— is preferred.Symbol n is an integer of 1 to 3. When n is 1, 2 or 3, the desiredaction is most characteristically exhibited. Methylene where n is 1,ethylene where n is 2 and trimethylene where n is 3 are preferred, andethylene where n is 2 is particularly preferred.

The unsaturated hydrocarbon chain having 2 or 3 carbon atoms means ahydrocarbon chain which contains an unsaturated bond as a double bond ora triple bond among the carbon-carbon bonds. As the unsaturatedhydrocarbon chain, an unsaturated hydrocarbon chain containing a doublebond is preferred. When the chain contains one or more double bonds, thenumber of the double bond may preferably one. Specific examples includeethenylene which has two carbon atoms and contains one double bond, aswell as ethynylene which has two carbon atoms and contains one triplebond, propen-3-yl which has three carbon atoms and contains one doublebond, and propyn-3-yl which has three carbon atoms and contains onetriple bond.

C², C³, C⁴, C⁵ and C⁶ in the aromatic ring (E) in the formula (I) eachrepresent a ring-constituting carbon atom. The ring-constituting carbonatoms form the aromatic ring (E), and accordingly, they are representedas C or CH. Among them, any one of ring-constituting carbon atoms towhich Rs or Ar does not bind may be replaced with V. The aforementionedexpression “to be replaced with” means that any one of thering-constituting carbon atoms C², C³, C⁴, C⁵ and C⁶ is replaced with V,and thus V may sometimes be a ring-constituting component. Rs and AReach bind to any of the ring-constituting carbon atoms C², C³, C⁴, C⁵ orC⁶ in the aromatic ring (E), and this means that, for example, when ARbinds to C², Rs binds to any of the ring-constituting carbon atoms C³,C⁴, C⁵ and C⁶, when AR binds to C³, Rs binds to any of thering-constituting carbon atoms C², C⁴, C⁵ and C⁶, and when AR bind toC⁴, Rs binds to the ring-constituting carbon atom C² or C³. Preferredexamples of these combinations of substitution positions include acompound wherein AR binds to C², and Rs binds to any of the atoms C³,C⁴, and C⁵, and particularly preferred examples include a compoundwherein AR binds to C², and Rs binds to C³ or C⁴. Preferred examplesalso include a compound wherein AR binds to C³, and Rs binds to any ofthe atoms C⁴, C⁵, and C⁶, and particularly preferred examples alsoinclude a compound wherein AR binds to C³, and Rs binds to the atom C⁴or C⁵. A still more preferred example is a compound wherein AR binds toC³, and Rs binds to C⁴.

One of the atoms C², C³, C⁴, C⁵ and C⁶ to which Rs and AR do not bindmay be replaced with V. For example, when AR binds to C², and Rs bindsto C³, one of the ring-constituting carbon atoms C⁴, C⁵, and C⁶ may bereplaced with V. As another example, it is meant that when AR binds toC³, and Rs binds to C⁴, one of the atoms C², C⁵, and C⁶ may be replacedwith V. Among them combinations and other combinations, preferredexamples are a compound wherein AR binds to C², Rs binds to C³, and C⁴is replaced with V; a compound wherein AR binds to C², Rs binds to C⁴,and C⁵ is replaced with V; a compound wherein AR binds to C², Rs bindsto C⁵, and C⁴ is replaced with V; a compound wherein AR binds to C³, Rsbinds to C⁴, and C⁵ is replaced with V; a compound wherein AR binds toC³, Rs binds to C⁴, and C⁵ is replaced with V; a compound wherein ARbinds to C³, Rs binds to C⁵, and C⁴ is replaced with V; a compoundwherein AR binds to C³, Rs binds to C⁶, and C⁵ is replaced with V, andthe like. Furthermore, particularly preferred examples include acompound wherein AR binds to C³, Rs binds to C⁴, and C⁵ is replaced withV; and a compound wherein AR binds to C³, Rs binds to C⁴, and C⁶ isreplaced with V, and an particularly preferred example is a compoundwherein AR binds to C³, Rs binds to C⁴, and C⁵ is replaced with V.

V represents nitrogen atom, or carbon atom substituted with Zx. Namely,when V represent nitrogen atom, the aromatic ring (E) in the formula (I)represents a pyridine ring. When V represent carbon atom substitutedwith Zx, the aromatic ring (E) is a benzene ring having Zx. Both of thecompounds are particularly preferred. Furthermore, a compound wherein ARbinds to C³, Rs binds to C⁴, C⁵ is V replaced with V, and this Vrepresents nitrogen atom is particularly preferred.

Zx is defined as a linear or branched saturated alkyl group having 1 to4 carbon atoms, fluorine atom, chlorine atom, bromine atom, nitro group,—OR⁹, or —N(Rn¹)(Rn²). Among them, fluorine atom, chlorine atom, bromineatom, and nitro group are preferred examples, and fluorine atom isparticularly preferred.

As for Zx, examples of the linear or branched saturated alkyl grouphaving 1 to 4 carbon atoms include methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group andthe like, and among them, methyl group is particularly preferred.

R⁹ represents hydrogen atom, a lower alkyl group having 1 to 4 carbonatoms, or -A⁶-Qp. Among them, hydrogen atom is a particularly preferredexample. Preferred examples of the lower alkyl group having 1 to 4carbon atoms include methyl group, ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, t-butyl group, and the like, andmethyl group is particularly preferred.

A⁶ in -A⁶-Qp represents a single bond or methylene, and Qp represents aphenyl group which may be substituted with one of T¹ or two or more ofthe same or different T¹. The substituent T¹ is a linear or branchedsaturated alkyl group having 1 to 4 carbon atoms, hydroxyl group,fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, nitrogroup, an alkoxy group having 1 to 4 carbon atoms, or a mono- ordialkylamino group having 1 to 4 carbon atoms. Specific examples of-A⁶-Qp include phenyl group, methylphenyl group, chlorophenyl group,benzyl group, methylbenzyl group, chlorobenzyl group, dichlorobenzylgroup, fluorobenzyl group, trifluoromethylbenzyl group, nitrobenzylgroup, methoxyphenyl group, N-methylaminobenzyl group,N,N-dimethylaminobenzyl group, and the like.

Preferred examples of —OR⁹ include hydroxyl group, methoxy group, andthe like, and hydroxyl group is particularly preferred.

Rn¹ represents hydrogen atom or a linear or branched saturated alkylgroup having 1 to 4 carbon atoms, and hydrogen atom is particularlypreferred. Examples of the linear or branched saturated alkyl grouphaving 1 to 4 carbon atoms include methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, or t-butyl group,and the like. Among them, methyl group, ethyl group, propyl group,isopropyl group, and the like are preferred examples, and methyl groupis particularly preferred.

Rn² has the same meaning as Rn¹, or represents a —COR²³ group or a—SO₂R²⁴ group, or binds to Rn¹ to form a 3- to 6-membered ring togetherwith the nitrogen atom to which they bind to form a saturatednitrogen-containing cycloalkyl group or morpholino group.

R²³ represents hydrogen atom, a lower alkyl group having 1 to 4 carbonatoms, a lower alkoxy group having 1 to 4 carbon atoms, —O-A⁶-Qp, or—N(R²⁵)(R²⁶). R²⁵ represents hydrogen atom, or a linear or branchedsaturated alkyl group having 1 to 4 carbon atoms, R²⁶ has the samemeaning as R²⁵, or binds to R²⁵ to form a 3- to 6-membered ring togetherwith the nitrogen atom to which they bind to represent a saturatednitrogen-containing cycloalkyl group or morpholino group. Examples ofthe compound wherein R²⁶ “binds to R²⁵ to form a 3- to 6-membered ringtogether with the nitrogen atom to which they bind to represent asaturated nitrogen-containing cycloalkyl group or morpholino group”include, for example, a compound wherein a cyclic aminoalkyl groupcontaining nitrogen atom such as pyrrolidino group, piperazino group andmorpholino group is formed.

Specific examples of —COR²³ include formyl group, acetyl group,t-butyloxycarbonyl group, phenyloxycarbonyl group, benzyloxycarbonylgroup, carbamoyl group, N-methylcarbamoyl group, N,N-dimethylcarbamoylgroup, piperidine-1-carbonyl group, morpholine-4-carbonyl group, and thelike, and preferred examples include formyl group, acetyl group,carbamoyl group, and the like. In the aforementioned formulas, asrepresented by A⁶ and Qp, for example, the same symbols may sometimes beused simultaneously at different positions. These symbols are used tomean the same class of groups of substituents. However, because eachsubstituent is independently chosen from each other, the same symbols donot mean that an identical substituent should be necessarily chosen, andas a result, selection of the same or different kind of substituent isnot prohibited.

R²⁴ represents a lower alkyl group having 1 to 4 carbon atoms, aminogroup, or a mono- or dialkylamino group having 1 to 4 carbon atoms.Specific examples of —SO₂R²⁴ include mesyl group, sulfamoyl group,N-methylsulfamoyl group, N,N-dimethylsulfamoyl group, and the like, andpreferred examples include mesyl group, N,N-dimethylsulfamoyl group, andthe like.

Specific examples of —N(Rn¹)(Rn²) include amino group, N-methylaminogroup, N-ethylamino group, N-propylamino group, N-isopropylamino group,N,N-dimethylamino group, N,N-diethylamino group, piperidino group,pyrrolidino group, morpholino group, formylamino group, acetylaminogroup, t-butyloxycarbonylamino group, phenyloxycarbonylamino group,benzyloxycarbonylamino group, carbamoylamino group,N-methylcarbamoylamino group, N,N-dimethylcarbamoylamino group,piperidine-1-carbonylamino group, morpholine-4-carbonylamino group,mesylamino group, sulfamoylamino group, N-methylsulfamoylamino group,N,N-dimethylsulfamoylamino group, and the like. Among them, preferredexamples include amino group, N-methylamino group, N-ethylamino group,N-propylamino group, N-isopropylamino group, N,N-dimethylamino group,N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, N,N-dimethylsulfamoylaminogroup, and the like, and amino group, N-methylamino group, andN,N-dimethylamino group are particularly preferred.

Therefore, preferred examples of Zx include fluorine atom, chlorineatom, bromine atom, nitro group, methyl group, hydroxyl group, methoxygroup, amino group, N-methylamino group, N-ethylamino group,N-propylamino group, N-isopropylamino group, N,N-dimethylamino group,N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, N,N-dimethylsulfamoylaminogroup, and the like, and particularly preferred examples includefluorine atom, methyl group, hydroxyl group, amino group, N-methylaminogroup, N,N-dimethylamino group, and the like.

In the formula (I), Rs is defined to represent -D-Rx or —N(Ry)(Rz).

D is defined to represent a single bond, oxygen atom, sulfur atom,—S(O)—, —S(O)₂—, or —C(O)—. Among them, oxygen atom and sulfur atom arepreferred, and oxygen atom is particularly preferred. Another preferredexamples include the compounds wherein D represent a single bond.

Rx represents a linear or branched saturated alkyl group having 3 to 8carbon atoms, or represents Ra, Rb, or Rc mentioned above.

As for Rx, examples of the linear or branched saturated alkyl grouphaving 3 to 8 carbon atoms include; for example, propyl group, isopropylgroup, butyl group, isobutyl group, 1-methylpropyl group, t-butyl group,pentyl group, isopentyl group, 2-methylbutyl group, 2,2-dimethylpropylgroup, hexyl group, 4-methylpentyl group, 2,3-dimethylbutyl group,2-ethylbutyl group, heptyl group, octyl group, and the like, and butylgroup, isobutyl group, and 2-ethylbutyl group are particularlypreferred.

As for Rx, R¹ of Ra is defined to be a saturated cyclic alkyl grouphaving 3 to 7 carbon atoms substituted with a lower alkyl group having 1to 4 carbon atoms or an unsubstituted saturated cyclic alkyl grouphaving 3 to 7 carbon atoms, or a condensed saturated cyclic alkyl grouphaving 6 to 8 carbon atoms substituted with a lower alkyl group having 1to 4 carbon atoms or an unsubstituted condensed saturated cyclic alkylgroup having 6 to 8 carbon atoms. As for R¹, examples of the saturatedcyclic alkyl group having 3 to 7 carbon atoms include cyclopropyl group,cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, and the like, and cyclopentyl group, cyclohexyl group, andcycloheptyl group are particularly preferred. As for R¹, examples of thecondensed saturated cyclic alkyl group having 6 to 8 carbon atoms groupinclude bicyclo[2,2,1]heptyl group, bicyclo[2,2,2]octyl group, and thelike.

Examples of the lower alkyl group having 1 to 4 carbon atomssubstituting on R¹ include methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, and thelike. Examples of R¹ substituted with a lower alkyl group having 1 to 4carbon atoms include methylcyclopentyl group, methylcyclohexyl group,methylbicyclo[2,2,1]heptyl group, and the like.

Symbol k is defined to be 0 or an integer of 1 to 3. A single bond wherek is 0, methylene where k is 1, and ethylene where k is 2 are preferred,and a bond where k is 0, and methylene where k is 1 are particularlypreferred.

Examples of Ra include cyclopropyl group, cyclobutyl group, cyclopentylgroup, cyclohexyl group, cycloheptyl group, cyclopropylmethyl group,cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group,cycloheptylmethyl group, 2-cyclopentylethyl group, 2-cyclohexylethylgroup, 3-cyclohexylpropyl group, 2-methylcyclopentyl group,3-methylcyclopentyl group, 3,4-dimethylcyclopentyl group,4-methylcyclohexyl group, 4,4-dimethylcyclohexyl group,4-ethylcyclohexyl group, 4-methylcyclohexylmethyl group,bicyclo[2,2,1]heptane-2-methyl group, bicyclo[2,2,2]octane-2-methylgroup, 3-methylbicyclo[2,2,1]heptane-2-methyl group,bicyclo[2,2,1]hept-1-ylmethyl group, bicyclo[2,2,2]oct-1-ylmethyl group,and the like. Cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, 2-cyclohexylethyl group are preferred, and cyclopentyl group,cyclohexyl group, cycloheptyl group, cyclopentylmethyl group,cyclohexylmethyl group are particularly preferred.

As for Rx, A² in Rb is defined to be a single bond, oxygen atom, sulfuratom, —S(O)—, —S(O)₂—, or —N(R⁴)—. R⁴ is defined to be a lower alkylgroup having 1 to 4 carbon atoms. Preferred examples are methyl group,ethyl group, propyl group, isopropyl group, butyl group, isobutyl group,t-butyl group, and the like, and methyl group and ethyl group areparticularly preferred examples. Therefore, particularly preferredexamples of A² include a single bond, oxygen atom, sulfur atom,—N(methyl)-, and —N(ethyl)-.

A¹ is defined to be a single bond or an alkylene (a) having 1 to 3carbon atoms, i.e., methylene, ethylene or trimethylene. However, whenA² represents oxygen atom, sulfur atom, —S(O)—, —S(O)₂— or —N(R⁴)—, A¹is ethylene or trimethylene Further, the alkylene (a) may be substitutedwith a lower alkyl group having 1 to 4 carbon atoms or phenyl group.Examples of the lower alkyl group having 1 to 4 carbon atoms for theabove compound include methyl group, ethyl group, propyl group,isopropyl group, butyl group, isobutyl group, t-butyl group, and thelike, and methyl group, and ethyl group are preferred examples. Specificexamples of A¹ include methylene, methylmethylene, ethylmethylene,phenylmethylene, ethylene, methylethylene, dimethylethylene,ethylethylene, phenylethylene, trimethylene, methyltrimethylene, and thelike. Among them, when A² represents a single bond, A¹ is mostpreferably a single bond, or methylene, methylmethylene, or ethylene.Further, when A² represents oxygen atom, sulfur atom, —S(O)—, —S(O)₂— or—N(R⁴)—, A¹ is most preferably ethylene.

Q in Rb is defined to be a residue of a partially unsaturated orcompletely unsaturated monocyclic or condensed bicyclic carbon ring orheterocyclic ring (q), and the heterocyclic ring (q) means a ringcontaining 1 to 4 the same or different ring-constituting heteroatomsselected from the group consisting of nitrogen atom, oxygen atom, andsulfur atom. The term “residue” means a monovalent group formed byeliminating hydrogen atom bonding to a ring-constituting atom. Theresidue of monocyclic carbon ring or heterocyclic ring is a partiallyunsaturated or completely unsaturated substituent having 5 to 7 atoms,and examples include, for example, phenyl group, thienyl group, furylgroup, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group,thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group,oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolylgroup, and the like. Among them, phenyl group, thienyl group, furylgroup, pyridyl group, and oxazolyl group are preferred examples, andphenyl group is particularly preferred.

The condensed bicyclic carbon ring or heterocyclic ring is a partiallyunsaturated or completely unsaturated ring having 8 to 11 atoms, andexamples of residue thereof include, for example, naphthyl group,tetrahydronaphthyl group, indanyl group, indenyl group, quinolyl group,isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group,benzimidazolyl group, benzoxazolyl group, benzothiazolyl group,indazolyl group, 4H-chromenyl group, dihydrobenzodioxyl group,benzoisoxazolyl group, pyrrolopyridinyl group, pyrazolopyridinyl group,triazolopyridinyl group, thienopyridinyl group, thienopyrazolyl group,1,3-dihydrobenzimidazole group, dihydro-3H-benzoxazole group,dihydro-3H-benzothiazole group, and the like. Among them, naphthylgroup, tetrahydronaphthyl group, indanyl group, indolyl group, anddihydrobenzodioxyl group are preferred examples, and indanyl group isone of particularly preferred examples.

Q binds to A² at an arbitrary position on the ring. Preferred examplesof Q with indication of bonding position include phenyl group, 2- or3-thienyl group, 2- or 3-furyl group, 2-, 3- or 4-pyridyl group, 2-, 4-or 5-oxazolyl group, 1- or 2-naphthyl group, 1-, 2-, 5- or6-tetrahydronaphthyl group, indan-1-yl group, indan-2-yl group,indan-4-yl group, indan-5-yl group, 1-, 2-, 3-, 4-, 5-, 6-, or 7-indolylgroup, 2-, 5- or 6-dihydrobenzodioxyl group, and the like. Among them,phenyl group, and indan-2-yl group are particularly preferred.

In Rb, R² and R³ are defined to be substituents of Q, and independentlyrepresent hydrogen atom, a linear or branched saturated alkyl grouphaving 1 to 4 carbon atoms, oxo group, thioxo group, fluorine atom,chlorine atom, bromine atom, trifluoromethyl group, —OR⁵, —N(R⁶)(R⁶′),—NHCOR⁷, —NHSO₂R⁸, or -A⁶-Qa, or bind to each other to representmethylenedioxy group.

Examples of the linear or branched saturated alkyl group having 1 to 4carbon atoms include methyl group, ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, t-butyl group, and the like, andmethyl group is particularly preferred.

R⁶ in —N(R⁶)(R⁶′) represents hydrogen atom or a lower alkyl group having1 to 4 carbon atoms. R⁶′ has the same meaning as R⁶, or binds to R⁶ toform a 3- to 6-membered ring together with the nitrogen atom to whichthey bind to form a saturated nitrogen-containing cycloalkyl group ormorpholino group. Therefore, specific examples of —N(R⁶)(R⁶′) includeamino group, N-methylamino group, N-ethylamino group, N-propylaminogroup, N-isopropylamino group, N,N-dimethylamino group, N,N-diethylaminogroup, piperidino group, pyrrolidino group, morpholino group, and thelike. N,N-Dimethylamino group, piperidino group, morpholino group, andthe like are preferred examples, and N,N-dimethylamino group is aparticularly preferred example.

R⁵ and R⁷ are defined to independently represent hydrogen atom, a loweralkyl group having 1 to 4 carbon atoms, or a -A⁶-Qa group. Examples ofthe lower alkyl group having 1 to 4 carbon atoms include methyl group,ethyl group, propyl group, isopropyl group, butyl group, isobutyl group,t-butyl group, and the like, and among them, methyl group is a preferredexample.

A⁶ in -A⁶-Qa has the same meaning as that defined above. Qa is definedto be a partially unsaturated or completely unsaturated monocyclic orcondensed bicyclic carbon ring or heterocyclic ring (qa), and theheterocyclic ring (qa) means a substituent containing 1 to 4 the same ordifferent ring-constituting heteroatoms selected from the groupconsisting of nitrogen atom, oxygen atom, and sulfur atom. Themonocyclic carbon ring or heterocyclic ring is a partially unsaturatedor completely unsaturated ring having 5 to 7 atoms, and examples ofresidue thereof include, for example, phenyl group, thienyl group, furylgroup, pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group,thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group,oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolylgroup, and the like. The condensed bicyclic carbon ring or heterocyclicring is a partially unsaturated or completely unsaturated ring having 8to 11 atoms, and examples of residue thereof include, for example,naphthyl group, indanyl group, indenyl group, quinolyl group,isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group,benzimidazolyl group, benzoxazolyl group, benzothiazolyl group,indazolyl group, and the like.

Qa binds to A⁶ at an arbitrary position on the ring. Further, Qa may besubstituted with two or more of the same or different T¹. T¹ has thesame meaning as defined above.

Specific examples of -A⁶-Qa include phenyl group, methylphenyl group,chlorophenyl group, benzyl group, methylbenzyl group, chlorobenzylgroup, dichlorobenzyl group, fluorobenzyl group, trifluoromethylbenzylgroup, nitrobenzyl group, methoxyphenyl group, N-methylaminobenzylgroup, N,N-dimethylaminobenzyl group, furyl group, thienyl group,pyrrolyl group, pyridyl group, oxazolyl group, isoxazolyl group,thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group,oxadiazolyl group, thiadiazolyl group, triazolyl group, tetrazolylgroup, naphthyl group, indanyl group, indenyl group, quinolyl group,isoquinolyl group, indolyl group, benzofuryl group, benzothienyl group,benzimidazolyl group, benzoxazolyl group, benzothiazolyl group,indazolyl group, and the like.

R⁸ each defined to be a lower alkyl group having 1 to 4 carbon atoms,and examples of the lower alkyl group having 1 to 4 carbon atoms includemethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, t-butyl group, and the like.

Therefore, preferred examples of R² and R³ include hydrogen atom, methylgroup, fluorine atom, chlorine atom, trifluoromethyl group, methoxygroup, dimethylamino group, acetylamino group, and methylsulfonylaminogroup, and hydrogen atom, methyl group, fluorine atom, chlorine atom,trifluoromethyl group, methoxy group, and dimethylamino group areparticularly preferred. When Q represents phenyl group, A¹ represents asingle bond, or unsubstituted methylene, and A² represents a singlebond, at least one of R² and R³ preferably represents a substituentother than hydrogen atom.

Particularly preferred examples of Rb include 2-methylphenyl group,4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3 (trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, and the like.

Symbol p in Rc is defined to be an integer of 2 to 4. Ethylene where pis 2, and trimethylene where p is 3 are preferred, and ethylene where pis 2 is particularly preferred. A⁴ represents a single bond, orrepresents methylene or ethylene, and a single bond and methylene areparticularly preferred. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—, andall of them are preferred. Rd represents hydrogen atom, an alkyl grouphaving 1 to 8 carbon atoms, or group Qa. Re represents an alkyl grouphaving 1 to 8 carbon atoms, a -A⁶-Qa group, a —(CH₂)_(i)R¹⁴ group, a—OR²⁸ group, a —SR²⁸ group, or a —N(R²⁹)(R³⁰) group. The group Qa and-A⁶-Qa have the same meanings as defined above.

The alkyl group having 1 to 8 carbon atoms is a linear or branchedsaturated alkyl group or a linear or branched partially unsaturatedalkyl group, or an alkyl group which may contain a cycloalkyl grouphaving 3 to 7 carbon atoms, and examples include, for example, methylgroup, ethyl group, propyl group, isopropyl group, butyl group, isobutylgroup, t-butyl group, pentyl group, isopentyl group, 2-methylbutylgroup, 2,2-dimethylpropyl group, hexyl group, 4-methylpentyl group,2,3-dimethylbutyl group, 2-ethylbutyl group, heptyl group, octyl group,cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopropylmethyl group, cyclobutylmethylgroup, cyclopentylmethyl group, cyclohexylmethyl group,cycloheptylmethyl group, 2-cyclopentylethyl group, 2-cyclohexylethylgroup, 2-methylcyclopentyl group, 3-methylcyclopentyl group,3,4-dimethylcyclopentyl group, 4-methylcyclohexyl group,4,4-dimethylcyclohexyl group, 4-ethylcyclohexyl group,4-methylcyclohexylmethyl group, and the like.

Symbol i in —(CH₂)_(i)R¹⁴ represents an integer of 1 to 3, and R¹⁴represents hydroxyl group, an alkoxy group having 1 to 4 carbon atoms,carboxyl group, or an N,N-dialkylcarbamoyl group having 1 to 4 carbonatoms. Examples of the alkoxy group having 1 to 4 carbon atoms includemethoxy group, ethoxy group, propyloxy group, isopropyloxy group, butoxygroup, isobutyloxy group, t-butyloxy group, and the like. Examples ofthe N,N-dialkylcarbamoyl group having 1 to 4 carbon atoms includeN,N-dimethylcarbamoyl group, N,N-diethylcarbamoyl group, and the like.

R²⁸ in —OR²⁸ or —SR²⁸ represents an alkyl group having 1 to 8 carbonatoms, or -A⁶-Qa, and these have the same meanings as defined above.

R²⁹ in —N(R²⁹)(R³⁰) represents an alkyl group having 1 to 8 carbonatoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, or -A⁶-Qa.Among them, the alkyl group having 1 to 8 carbon atoms and -A⁶-Qa havethe same meanings as those defined above. Examples of the alkoxycarbonylgroup having 1 to 4 carbon atoms include methyloxycarbonyl group,ethyloxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonylgroup, butyloxycarbonyl group, isobutyloxycarbonyl group,t-butyloxycarbonyl group, and the like. R³⁰ represents hydrogen atom ora lower alkyl group having 1 to 4 carbon atoms, or binds to R²⁹ to forma 3- to 6-membered ring together with the nitrogen atom to which theybind to form a saturated nitrogen-containing cycloalkyl group ormorpholino group. The lower alkyl group having 1 to 4 carbon atoms hasthe same meaning as defined above. Examples of the compound where “R³⁰binds to R²⁹ to form a 3- to 6-membered ring together with the nitrogenatom to which they bind to form a saturated nitrogen-containingcycloalkyl group or morpholino group” include, for example, a compoundwherein a cyclic aminoalkyl group containing nitrogen atom such aspyrrolidino group, piperazino group, and morpholino group is formed.

Preferred examples of Rd include hydrogen atom as well as methyl group,ethyl group, propyl group, isopropyl group, butyl group, isobutyl group,cyclopropyl group, cyclopropylmethyl group, cyclopentyl group,cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group,phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenylgroup, benzyl group, 4-chlorobenzyl group, 4-fluorobenzyl group,pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, and thelike.

Particularly preferred examples of Rd include methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenylgroup, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, and the like.

Preferred examples of substituted -A⁴-Rd include methyl group, ethylgroup, propyl group, isopropyl group, butyl group, isobutyl group,pentyl group, isoamyl group, cyclopropyl group, cyclopropylmethyl group,2-(cyclopropyl)ethyl group, cyclopentyl group, cyclopentylmethyl group,2-(cyclopentyl)ethyl group, cyclohexyl group, cyclohexylmethyl group,2-(cyclohexyl)ethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group,2-(4-chlorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,(pyridin-2-yl)methyl group, (pyridin-3-yl)methyl group,(pyridin-4-yl)methyl group, and the like.

Particularly preferred examples of substituted -A⁴-Rd include methylgroup, ethyl group, propyl group, isopropyl group, butyl group, isobutylgroup, pentyl group, isoamyl group, cyclopropyl group, cyclopropylmethylgroup, cyclopentyl group, cyclopentylmethyl group, cyclohexyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group,2-(4-chlorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group, and thelike.

Preferred examples of Re include methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group,cyclopropyl group, cyclopentyl group, cyclohexyl group,cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethylgroup, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-ylgroup, methoxy group, ethoxy group, propyloxy group, isopropyloxy group,butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxygroup, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxygroup, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxygroup, 4-chlorophenyloxy group, 4-fluorophenyloxy group, methylthioxogroup, amino group, N-methylamino group, N,N-dimethylamino group,N-ethylamino group, N,N-diethylamino group, N-propylamino group,N-isopropylamino group, N-butylamino group, N-isobutylamino group,N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylaminogroup, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,ethyloxycarbonylamino group, and the like.

Particularly preferred examples of Re include isopropyl group, butylgroup, isobutyl group, t-butyl group, cyclopropyl group, cyclopentylgroup, cyclohexyl group, cyclopentylmethyl group, cyclohexylmethylgroup, phenyl group, 4-methylphenyl group, 4-chlorophenyl group,4-fluorophenyl group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, N-propylamino group,N-isopropylamino group, N-butylamino group, N-isobutylamino group,N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylaminogroup, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, pyrrolidino group, piperidino group,morpholino group, and the like.

Preferred examples of -A⁵-Re include acetyl group, thioacetyl group,methanesulfonyl group, propionyl group, ethylthiocarbonyl group, butyrylgroup, propylthiocarbonyl group, isobutyryl group, isopropylthiocarbonylgroup, isopropylsulfonyl group, valeryl group, butylthiocarbonyl group,isovaleryl group, isobutylthiocarbonyl group, pivaloyl group,t-butylthiocarbonyl group, cyclopropylcarbonyl group,cyclopropylthiocarbonyl group, cyclopentylcarbonyl group,cyclopentylthiocarbonyl group, cyclohexylcarbonyl group,cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group,cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group,cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group,phenylsulfonyl group, 4-methylphenylcarbonyl group,4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group,4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group,4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group,phenylmethylcarbonyl group, 4-methylphenylmethylcarbonyl group,4-chlorophenylmethylcarbonyl group, 4-fluorophenylmethylcarbonyl group,(pyridin-2-yl)carbonyl group, (pyridin-2-yl)thiocarbonyl group,(pyridin-3-yl)carbonyl group, (pyridin-4-yl)carbonyl group,(furan-2-yl)carbonyl group, (thiophen-2-yl)carbonyl group,methyloxycarbonyl group, methylsulfanylcarbonyl group,methyloxythiocarbonyl group, methyloxycarbonylaminocarbonyl group,carbamoyl group, N-methylcarbamoyl group, N-methylthiocarbamoyl group,N,N-dimethylcarbamoyl group, N,N-dimethylthiocarbamoyl group,N,N-dimethylsulfamoyl group, ethyloxycarbonyl group,ethyloxycarbonylaminocarbonyl group, N-ethylcarbamoyl group,N-ethylthiocarbamoyl group, N,N-diethylcarbamoyl group,N,N-diethylthiocarbamoyl group, N,N-diethylsulfamoyl group,propyloxycarbonyl group, N-propylcarbamoyl group, N-propylthiocarbamoylgroup, isopropyloxycarbonyl group, N-isopropylcarbamoyl group,N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoylgroup, N-butylthiocarbamoyl group, isobutyloxycarbonyl group,N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group,t-butyloxycarbonyl group, N-t-butylcarbamoyl group,N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group,N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group,cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group,N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group,N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group,cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group,phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoylgroup, 4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoylgroup, N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonylgroup, N-(4-chlorophenyl)carbamoyl group,N-(4-chlorophenyl)thiocarbamoyl group, 4-fluorophenyloxycarbonyl group,N-(4-fluorophenyl)carbamoyl group, N-(4-fluorophenyl)thiocarbamoylgroup, phenylmethyloxycarbonyl group, 4-methylphenylmethyloxycarbonylgroup, 4-chlorophenylmethyloxycarbonyl group,4-fluorophenylmethyloxycarbonyl group, N-(pyridin-2-yl)carbamoyl group,N-(pyridin-2-yl)thiocarbamoyl group, N-(pyridin-3-yl)carbamoyl group,N-(pyridin-3-yl)thiocarbamoyl group, N-(pyridin-4-yl)carbamoyl group,N-(pyridin-4-yl)thiocarbamoyl group, N-(furan-2-yl)carbamoyl group,N-(thiophen-2-yl)carbamoyl group, (pyrrolidino-1-yl)carbonyl group,(piperidino-1-yl)carbonyl group, (morpholino-4-yl)carbonyl group, andthe like.

Particularly preferred examples of -A⁵-Re include isobutyryl group,isopropylthiocarbonyl group, isopropylsulfonyl group, valeryl group,butylthiocarbonyl group, isovaleryl group, isobutylthiocarbonyl group,pivaloyl group, t-butylthiocarbonyl group, cyclopropylcarbonyl group,cyclopropylthiocarbonyl group, cyclopentylcarbonyl group,cyclopentylthiocarbonyl group, cyclohexylcarbonyl group,cyclohexylthiocarbonyl group, cyclopentylmethylcarbonyl group,cyclopentylmethylthiocarbonyl group, cyclohexylmethylcarbonyl group,cyclohexylmethylthiocarbonyl group, benzoyl group, thiobenzoyl group,phenylsulfonyl group, 4-methylphenylcarbonyl group,4-methylphenylthiocarbonyl group, 4-methylphenylsulfonyl group,4-chlorophenylcarbonyl group, 4-chlorophenylthiocarbonyl group,4-fluorophenylcarbonyl group, 4-fluorophenylthiocarbonyl group,isopropyloxycarbonyl group, N-isopropylcarbamoyl group,N-isopropylthiocarbamoyl group, butyloxycarbonyl group, N-butylcarbamoylgroup, N-butylthiocarbamoyl group, isobutyloxycarbonyl group,N-isobutylcarbamoyl group, N-isobutylthiocarbamoyl group,t-butyloxycarbonyl group, N-t-butylcarbamoyl group,N-t-butylthiocarbamoyl group, cyclopropyloxycarbonyl group,N-cyclopropylcarbamoyl group, N-cyclopropylthiocarbamoyl group,cyclopentyloxycarbonyl group, N-cyclopentylcarbamoyl group,N-cyclopentylthiocarbamoyl group, cyclohexyloxycarbonyl group,N-cyclohexylcarbamoyl group, N-cyclohexylthiocarbamoyl group,cyclopentylmethyloxycarbonyl group, cyclohexylmethyloxycarbonyl group,phenyloxycarbonyl group, N-phenylcarbamoyl group, N-phenylthiocarbamoylgroup, 4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoylgroup, N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonylgroup, N-(4-chlorophenyl)carbamoyl group,N-(4-chlorophenyl)thiocarbamoyl group, 4-fluorophenyloxycarbonyl group,N-(4-fluorophenyl)carbamoyl group, N-(4-fluorophenyl)thiocarbamoylgroup, (pyrrolidino-1-yl)carbonyl group, (piperidino-1-yl)carbonylgroup, (morpholino-4-yl)carbonyl group, and the like.

Specific examples of Rc include 2-(N-isobutyryl-N-methylamino)ethylgroup, 2-(N-ethyl-N-isobutyrylamino)ethyl group,2-(N-isobutyryl-N-propylamino)ethyl group,2-(N-isobutyryl-N-isopropylamino)ethyl group,2-(N-butyl-N-isobutyrylamino)ethyl group,2-(N-isobutyl-N-isobutyrylamino)ethyl group,2-(N-cyclopropyl-N-isobutyrylamino)ethyl group,2-(N-cyclopentyl-N-isobutyrylamino)ethyl group,2-(N-cyclopentylmethyl-N-isobutyrylamino)ethyl group,2-(N-cyclohexyl-N-isobutyrylamino)ethyl group,2-(N-cyclohexylmethyl-N-isobutyrylamino)ethyl group,2-(N-isobutyryl-N-phenylamino)ethyl group,2-[N-isobutyryl-N-(4-methylphenyl)amino]ethyl group,2-[N-(4-chlorophenyl)-N-isobutyrylamino]ethyl group,2-[N-(4-fluorophenyl)-N-isobutyrylamino]ethyl group,2-(N-benzyl-N-isobutyrylamino)ethyl group,2-[N-(4-chlorophenylmethyl)-N-isobutyrylamino]ethyl group,2-[N-(4-fluorophenylmethyl)-N-isobutyrylamino]ethyl group,2-[N-[2-(4-chlorophenyl)ethyl]-N-isobutyrylamino]ethyl group,2-[N-[2-(4-fluorophenyl)ethyl]-N-isobutyrylamino]ethyl group,2-(N-isobutylthiocarbonyl-N-methylamino)ethyl group,2-(N-isobutylthiocarbonyl-N-isopropylamino)ethyl group,2-(N-butyl-N-isobutylthiocarbonylamino)ethyl group,2-(N-isobutyl-N-isobutylthiocarbonylamino)ethyl group,2-(N-cyclopentyl-N-isobutylthiocarbonylamino)ethyl group,2-(N-cyclopentylmethyl-N-isobutylthiocarbonylamino)ethyl group,2-(N-isobutylthiocarbonyl-N-phenylamino)ethyl group,2-(N-benzyl-N-isobutylthiocarbonylamino)ethyl group,2-[N-(4-fluorophenylmethyl)-N-isobutylthiocarbonylamino]ethyl group,2-(N-methyl-N-pivaloylamino)ethyl group,2-(N-isopropyl-N-pivaloylamino)ethyl group,2-(N-butyl-N-pivaloylamino)ethyl group,2-(N-isobutyl-N-pivaloylamino)ethyl group,2-(N-cyclohexyl-N-pivaloylamino)ethyl group,2-(N-cyclohexylmethyl-N-pivaloylamino)ethyl group,2-(N-phenyl-N-pivaloylamino)ethyl group,2-(N-benzyl-N-pivaloylamino)ethyl group,2-(N-cyclopentylcarbonyl-N-methylamino)ethyl group,2-(N-butyl-N-cyclopentylcarbonylamino)ethyl group,2-(N-cyclopentylcarbonyl-N-isobutylamino)ethyl group,2-(N-cyclopentylcarbonyl-N-cyclopentylmethylamino)ethyl group,2-(N-cyclopentylcarbonyl-N-phenylamino)ethyl group,2-[N-cyclopentylcarbonyl-N-(4-fluorophenyl)amino]ethyl group,2-(N-benzyl-N-cyclopentylcarbonylamino)ethyl group,2-[N-cyclopentylcarbonyl-N-(4-fluorophenylmethyl)amino]ethyl group,2-(N-methyl-N-phenylsulfonylamino)ethyl group,2-(N-ethyl-N-phenylsulfonylamino)ethyl group,2-(N-phenylsulfonyl-N-propylamino)ethyl group,2-(N-isopropyl-N-phenylsulfonylamino)ethyl group,2-(N-butyl-N-phenylsulfonylamino)ethyl group,2-(N-isobutyl-N-phenylsulfonylamino)ethyl group,2-(N-cyclopropyl-N-phenylsulfonylamino)ethyl group,2-(N-cyclopentyl-N-phenylsulfonylamino)ethyl group,2-(N-cyclopentylmethyl-N-phenylsulfonylamino)ethyl group,2-(N-cyclohexyl-N-phenylsulfonylamino)ethyl group,2-(N-cyclohexylmethyl-N-phenylsulfonylamino)ethyl group,2-(N-phenyl-N-phenylsulfonylamino)ethyl group,2-[N-(4-fluorophenyl)-N-phenylsulfonylamino]ethyl group,2-(N-benzyl-N-phenylsulfonylamino)ethyl group,2-[N—(N-butylcarbamoyl)-N-methylamino]ethyl group,2-[N-butyl-N—(N-butylcarbamoyl)amino]ethyl group,2-[N—(N-butylcarbamoyl)-N-isobutylamino]ethyl group,2-[N—(N-butylcarbamoyl)-N-cyclopentylamino]ethyl group,2-[N—(N-butylcarbamoyl)-N-cyclohexylmethylamino]ethyl group,2-[N—(N-butylcarbamoyl)-N-phenylamino]ethyl group,2-{N—(N-butylcarbamoyl)-N-(4-fluorophenyl)amino}ethyl group,2-[N-benzyl-N—(N-butylcarbamoyl)amino]ethyl group,2-{N—(N-butylcarbamoyl)-N-(4-fluorophenylmethyl)amino}ethyl group,2-{N—(N-butylcarbamoyl)-N-[2-(4-fluorophenyl)ethyl]amino}ethyl group,2-[N—(N-isopropylthiocarbamoyl)-N-methylamino]ethyl group,2-[N-butyl-N—(N-isopropylthiocarbamoyl)amino]ethyl group,2-[N-isobutyl-N—(N-isopropylthiocarbamoylamino]ethyl group,2-[N-cyclopentyl-N—(N-isopropylthiocarbamoyl)amino]ethyl group,2-[N-cyclohexylmethyl-N—(N-isopropylthiocarbamoyl)amino]ethyl group,2-[N—(N-isopropylthiocarbamoyl)-N-phenylamino]ethyl group,2-{N-(4-fluorophenyl)-N—(N-isopropylthiocarbamoyl)amino}ethyl group,2-[N-benzyl-N—(N-isopropylthiocarbamoyl)amino]ethyl group,2-(N-isobutyloxycarbonyl-N-methylamino)ethyl group,2-(N-butyl-N-isobutyloxycarbonylamino)ethyl group,2-(N-isobutyl-N-isobutyloxycarbonylamino)ethyl group,2-(N-cyclopentyl-N-isobutyloxycarbonylamino)ethyl group,2-(N-cyclohexylmethyl-N-isobutyloxycarbonylamino)ethyl group,2-(N-isobutyloxycarbonyl-N-phenylamino)ethyl group,2-[N-(4-fluorophenyl)-N-isobutyloxycarbonylamino]ethyl group,2-(N-benzyl-N-isobutyloxycarbonylamino)ethyl group,2-[N—(N-cyclopentylcarbamoyl)-N-methylamino]ethyl group,2-[N-butyl-N—(N-cyclopentylcarbamoyl)amino]ethyl group,2-[N—(N-cyclopentylcarbamoyl)-N-isobutylamino]ethyl group,2-[N-cyclopentyl-N—(N-cyclopentylcarbamoyl)amino]ethyl group,2-[N-cyclohexylmethyl-N—(N-cyclopentylcarbamoyl)amino]ethyl group,2-[N—(N-cyclopentylcarbamoyl)-N-phenylamino]ethyl group,2-[N-benzyl-N—(N-cyclopentylcarbamoyl)amino]ethyl group,2-[N—(N-cyclohexylthiocarbamoyl)-N-methylamino]ethyl group,2-[N-butyl-N—(N-cyclohexylthiocarbamoyl)amino]ethyl group,2-[N—(N-cyclohexylthiocarbamoyl)-N-isobutylamino]ethyl group,2-[N—(N-cyclohexylthiocarbamoyl)-N-cyclopentylamino]ethyl group,2-[N-cyclohexylmethyl-N—(N-cyclohexylthiocarbamoyl)amino]ethyl group,2-[N—(N-cyclohexylthiocarbamoyl)-N-phenylamino]ethyl group,2-[N-benzyl-N—(N-cyclohexylthiocarbamoyl)amino]ethyl group,2-(N-methyl-N-phenyloxycarbonylamino)ethyl group,2-(N-butyl-N-phenyloxycarbonylamino)ethyl group,2-(N-isobutyl-N-phenyloxycarbonylamino)ethyl group,2-(N-cyclopentyl-N-phenyloxycarbonylamino)ethyl group,2-(N-cyclohexylmethyl-N-phenyloxycarbonylamino)ethyl group,2-(N-phenyl-N-phenyloxycarbonylamino)ethyl group,2-(N-benzyl-N-phenyloxycarbonylamino)ethyl group,2-[N-methyl-N—(N-phenylcarbamoyl)amino]ethyl group,2-[N-butyl-N—(N-phenylcarbamoyl)amino]ethyl group,2-[N-isobutyl-N—(N-phenylcarbamoyl)amino]ethyl group,2-[N-cyclopentyl-N—(N-phenylcarbamoyl)amino]ethyl group,2-[N-cyclohexylmethyl-N—(N-phenylcarbamoyl)amino]ethyl group,2-[N-phenyl-N—(N-phenylcarbamoyl)amino]ethyl group,2-[N-benzyl-N—(N-phenylcarbamoyl)amino]ethyl group, and the like.

When Rs in the formula (I) represents —N(Ry)(Rz), Rz is defined to havethe same meaning as Rx, or Rz represents methyl group, ethyl group, or a-A⁵-Re group. -A⁵-Re has the same meaning as defined above.

Particularly preferred examples of Rz include butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, (morpholino-4-yl)carbonyl group,and the like.

Among the Rz, methyl group or ethyl group is particularly preferred whenRy is other than hydrogen atom.

Ry represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms,or a -A⁶-Qp group, or binds to Rz to form a saturated or unsaturatednitrogen-containing cyclic substituent having 3 to 7 atoms together withnitrogen atom to which they bind. The alkyl group having 1 to 8 carbonatoms is a linear or branched saturated alkyl group, a linear orbranched partially unsaturated alkyl group, or an alkyl group which maycontain a cyclic alkyl group having 3 to 7 carbon atoms. Examplesinclude methyl group, ethyl group, propyl group, isopropyl group, butylgroup, isobutyl group, t-butyl group, pentyl group, isopentyl group,2-methylbutyl group, 2,2-dimethylpropyl group, hexyl group,4-methylpentyl group, 2,3-dimethylbutyl group, 2-ethylbutyl group,heptyl group, octyl group, cyclopropyl group, cyclobutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethylgroup, cyclohexylmethyl group, cycloheptylmethyl group,2-cyclopentylethyl group, 2-cyclohexylethyl group, 2-methylcyclopentylgroup, 3-methylcyclopentyl group, 3,4-dimethylcyclopentyl group,4-methylcyclohexyl group, 4,4-dimethylcyclohexyl group,4-ethylcyclohexyl group, 4-methylcyclohexylmethyl group, and the like.-A⁶-Qp has the same meaning as defined above.

Particularly preferred examples of Ry include hydrogen atom, methylgroup, ethyl group, isobutyl group, and the like.

Ry also binds to Rz to represents a saturated or unsaturatednitrogen-containing cyclic substituent having 3 to 7 atoms formedtogether with the nitrogen atom to which they bind. Specific examplesthereof include cyclic substituents containing nitrogen atom such as1-pyrrolidino group, 1-piperidino group, 1-homopiperidino group,1-piperazino group, 4-morpholino group, pyrrol-1-yl group, imidazol-1-ylgroup, and pyrazol-1-yl group, and all of these are preferred.

The nitrogen-containing cyclic substituent may be substituted with oneor two lower alkyl groups having 1 to 4 carbon atoms wherein the twoalkyl groups may be the same or different. Examples of the lower alkylhaving 1 to 4 carbon atoms include methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, or t-butyl group.

Among the substituent —N(Ry)(Rz), particularly preferred examplesinclude N,N-dimethylamino group, N-ethyl-N-methylamino group,N,N-diethylamino group, N-methyl-N-propylamino group,N-ethyl-N-propylamino group, N-isopropyl-N-methylamino group,N-ethyl-N-isopropylamino group, N-butylamino group,N-butyl-N-methylamino group, N-butyl-N-ethylamino group, N-isobutylaminogroup, N-isobutyl-N-methylamino group, N-ethyl-N-isobutylamino group,N-(2-ethylbutyl)amino group, N-(2-ethylbutyl)-N-methylamino group,N-cyclopentylamino group, N-cyclopentyl-N-methylamino group,N-cyclohexylamino group, N-cyclohexyl-N-methylamino group,N-cycloheptylamino group, N-(cyclopentylmethyl)amino group,N-(cyclopentylmethyl)-N-methylamino group, N-(cyclohexylmethyl)aminogroup, N-(cyclohexylmethyl)-N-methylamino group, N-(2-methylphenyl)aminogroup, N-(4-methylphenyl)amino group, N-(2-fluorophenyl)amino group,N-(3-fluorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(2-chlorophenyl)amino group, N-(3-chlorophenyl)amino group,N-(4-chlorophenyl)amino group, N-(indan-2-yl)amino group,N-(1-phenylethyl)amino group, N-[1-(2-fluorophenyl)ethyl]amino group,N-[1-(3-fluorophenyl)ethyl]amino group, N-[1-(4-fluorophenyl)ethyl]aminogroup, N-[1-(2-chlorophenyl)ethyl]amino group,N-[1-(3-chlorophenyl)ethyl]amino group, N-[1-(4-chlorophenyl)ethyl]aminogroup, N-(2-methylphenylmethyl)amino group,N-methyl-N-(2-methylphenylmethyl)amino group,N-(3-methylphenylmethyl)amino group,N-methyl-N-(3-methylphenylmethyl)amino group,N-(4-methylphenylmethyl)amino group,N-methyl-N-(4-methylphenylmethyl)amino group,N-(2-fluorophenylmethyl)amino group,N-(2-fluorophenylmethyl)-N-methylamino group,N-(3-fluorophenylmethyl)amino group,N-(3-fluorophenylmethyl)-N-methylamino group,N-(4-fluorophenylmethyl)amino group,N-(4-fluorophenylmethyl)-N-methylamino group,N-(2-chlorophenylmethyl)amino group,N-(2-chlorophenylmethyl)-N-methylamino group,N-(3-chlorophenylmethyl)amino group, N-(3chlorophenylmethyl)-N-methylamino group, N-(4-chlorophenylmethyl)aminogroup, N-(4-chlorophenylmethyl)-N-methylamino group,N-(2,3-difluorophenylmethyl)amino group,N-(2,3-difluorophenylmethyl)-N-methylamino group,N-(2,4-difluorophenylmethyl)amino group,N-(2,4-difluorophenylmethyl)-N-methylamino group,N-(2,5-difluorophenylmethyl)amino group,N-(2,5-difluorophenylmethyl)-N-methylamino group,N-(3,4-difluorophenylmethyl)amino group,N-(3,4-difluorophenylmethyl)-N-methylamino group,N-(3,5-difluorophenylmethyl)amino group,N-(3,5-difluorophenylmethyl)-N-methylamino group,N-(2,3-dichlorophenylmethyl)amino group,N-(2,3-dichlorophenylmethyl)-N-methylamino group,N-(2,4-dichlorophenylmethyl)amino group,N-(2,4-dichlorophenylmethyl)-N-methylamino group,N-(2,5-dichlorophenylmethyl)amino group,N-(2,5-dichlorophenylmethyl)-N-methylamino group,N-(2,6-dichlorophenylmethyl)amino group,N-(2,6-dichlorophenylmethyl)-N-methylamino group,N-(3,4-dichlorophenylmethyl)amino group,N-(3,4-dichlorophenylmethyl)-N-methylamino group,N-(3,5-dichlorophenylmethyl)amino group,N-(3,5-dichlorophenylmethyl)-N-methylamino group,N-[2-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[2-(trifluoromethyl)phenylmethyl]amino group,N-[3-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[3-(trifluoromethyl)phenylmethyl]amino group,N-[4-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[4-(trifluoromethyl)phenylmethyl]amino group, 1-pyrrolidinogroup, 1-(4-methylpiperidino) group, 1-homopiperidino group, and4-morpholino group.

A most preferred example of Rs in the aforementioned general formula (I)include Rs which meets the conditions of: Rs is -D-Rx wherein D is asingle bond and Rx represents Rb, and A¹ and A² in Rb are single bonds.Specific examples include phenyl group, 2-methylphenyl group,3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group,3,5-dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group,4-methoxyphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, 2,3-difluorophenyl group, 2,4-difluorophenylgroup, 2,5-difluorophenyl group, 3,4-difluorophenyl group,2,3-dichlorophenyl group, 2,4-dichlorophenyl group, 2,5-dichlorophenylgroup, 2,6-dichlorophenyl group, 3,4-dichlorophenyl group,3,5-dichlorophenyl group, 2-trifluoromethylphenyl group,3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group,4-(N,N-dimethylamino)phenyl group, indan-2-yl group, 4-methylindan-2-ylgroup, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group,thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group,pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group,naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-1H-indol-5-ylgroup, 1H-indazol-5-yl group, or 1-methyl-1H-indazol-5-yl group.

AR in the formula (I) is defined to be a residue of a partiallyunsaturated or completely unsaturated condensed bicyclic carbon ring orheterocyclic ring (ar). Further, AR may be substituted with one of Xa ortwo or more of the same or different Xa. The heterocyclic ring (ar)means a ring containing 1 to 4 the same or different ring-constitutingheteroatoms selected from the group consisting of nitrogen atom, oxygenatom, and sulfur atom.

The “condensed bicyclic carbon ring or heterocyclic ring” means apartially unsaturated or completely unsaturated ring having 8 to 11atoms. Preferred examples include a partially unsaturated or completelyunsaturated ring consisting of 8 atoms formed by fusion of 5-memberedheterocyclic rings containing 1 or 2 ring-constituting heteroatomsselected from the group consisting of nitrogen, oxygen, and sulfuratoms, a partially unsaturated or completely unsaturated ring consistingof 9 atoms formed by fusion of a 5-membered heterocyclic ring containing1 or 2 ring-constituting heteroatoms selected from the group consistingof nitrogen, oxygen, and sulfur atoms and a 6-membered carbon ring or a6-membered heterocyclic ring containing 1 or 2 ring-constitutingheteroatoms selected from the group consisting of nitrogen, oxygen, andsulfur atoms, and a partially unsaturated or completely unsaturatedsubstituent consisting of 10 atoms formed by fusion of a 6-memberedcarbon ring or a 6-membered heterocyclic ring containing 1 or 2ring-constituting heteroatoms selected from the group consisting ofnitrogen, oxygen, and sulfur atoms and a 6-membered carbon ring or6-membered heterocyclic rings containing 1 or 2 ring-constitutingheteroatoms selected from, the group consisting of nitrogen, oxygen, andsulfur atom. As the carbon ring constituting AR not containing aheteroatom, among the rings constituting AR, naphthalene ring isparticularly preferred. Further, as the heterocyclic ring (ar)containing a heteroatom, among the rings constituting AR, thosecontaining 1 or 2 ring-constituting heteroatoms are preferred.

As for AR in the formula (I), specific examples of preferred ringconstituting AR include naphthalene, benzofuran, benzo[b]thiophene,indole, benzothiazole, dihydro-3H-benzothiazole, quinoline,dihydro-1H-quinoline, benzo[d]isothiazole, 1H-indazole,benzo[c]isothiazole, 2H-indazole, imidazo[1,2-a]pyridine,1H-pyrrolo[2,3-b]pyridine, isoquinoline, dihydro-2H-isoquinoline,cinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole,1H-pyrrolo[3,2-b]pyridine, benzo[1,2,5]thiadiazole, 1H-benzotriazole,1,3-dihydropyrrolo[2,3-b]pyridine, 1,3-dihydrobenzimidazole,dihydro-3H-benzoxazole, phthalazine, [1,8]naphthalidine,[1,5]naphthalidine, 1H-pyrrolo[3,2-c]pyridine,1H-pyrrolo[2,3-c]pyridine, 1H-pyrazolo[4,3-b]pyridine,1H-pyrazolo[4,3-c]pyridine, 1H-pyrazolo[3,4-c]pyridine,1H-pyrazolo[3,4-b]pyridine, [1,2,4]triazolo[4,3-a]pyridine,thieno[3,2-c]pyridine, thieno[3,2-b]pyridine, 1H-thieno[3,2-c]pyrazole,benzo[d]isoxazole, benzo[c]isoxazole, indolizine, 1,3-dihydroindol,1H-pyrazolo[3,4-d]thiazole, 2H-isoindol,[1,2,4]triazolo[1,5-a]pyrimidine, 1H-pyrazolo[3,4-b]pyrazine,1H-imidazo[4,5-b]pyrazine, 7H-purine, 4H-chromene, and the like. Amongthem, naphthalene, benzofuran, benzo[b]thiophene, indole, benzothiazole,dihydro-3H-benzothiazole, quinoline, dihydro-1H-quinoline,benzo[d]isothiazole, 1H-indazole, benzo[c]isothiazole, 2H-indazole,imidazo[1,2-a]pyridine, 1H-pyrrolo[2,3-b]pyridine, isoquinoline anddihydro-2H-isoquinoline constitute a particularly preferred group, andcinnoline, quinazoline, quinoxaline, 1H-benzimidazole, benzoxazole,1H-pyrrolo[3,2-b]pyridine, benzo[1,2,5]thiadiazole, 1H-benzotriazole,1,3-dihydropyrrolo[2,3-b]pyridine, 1,3-dihydrobenzimidazole anddihydro-3H-benzoxazole also constitute a particularly preferred group.Further, naphthalene, benzofuran, benzo[b]thiophene, indole,benzothiazole, quinoline, 1H-indazole and isoquinoline are particularlypreferred.

AR binds to any of the ring-constituting carbon atoms C², C³, C⁴, C⁵,and C⁶ in the aromatic ring (E) in the aforementioned formula (I) at anarbitrary carbon atom in AR. Preferred examples of the ring constitutingAR include, as indicated with substitution position in the aromatic ring(E), naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, 4H-chromen-5-ylgroup, and the like. Among them, naphthalen-2-yl group, naphthalen-1-ylgroup, benzofuran-5-yl group, benzofuran-4-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group, indol-5-ylgroup, indol-4-yl group, benzothiazol-6-yl group, benzothiazol-7-ylgroup, quinolin-6-yl group, quinolin-3-yl group,dihydro-1H-quinolin-6-yl group, benzo[d]isothiazol-5-yl group,1H-indazol-5-yl group, 1H-indazol-4-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-yl group,dihydro-2H-isoquinolin-6-yl group, cinnolin-6-yl group, benzoxazol-5-ylgroup, and the like constitute a particularly preferred group, andnaphthalen-2-yl group, benzofuran-5-yl group, benzo[b]thiophen-5-ylgroup, indol-5-yl group, benzothiazol-6-yl group, quinolin-6-yl group,quinolin-3-yl group, benzo[d]isothiazol-5-yl group, 1H-indazol-5-ylgroup, imidazo[1,2-a]pyridin-6-yl group, 1H-pyrrolo[2,3-b]pyridin-5-ylgroup, isoquinolin-6-yl group, cinnolin-6-yl group, benzoxazol-5-ylgroup and the like are particularly preferred.

Further, AR may be substituted with one of Xa or the same or differenttwo or more of Xa. Examples of substitution position of Xa include acarbon atom of AR not bonding to the aromatic ring (E), and/or whennitrogen atom is present, that nitrogen atom.

The substituent Xa represents a linear or branched saturated alkyl grouphaving 1 to 4 carbon atoms, a saturated cyclic alkyl group having 3 to 7carbon atoms, oxo group, thioxo group, fluorine atom, chlorine atom,trifluoromethyl group, —(CH₂)_(i)R¹⁴, —OR¹⁰, —N(R¹¹)(R¹²), —SO₂R¹³, or—COR²⁷. However, when nitrogen atom is present in AR, Xa which maysubstitute on the nitrogen atom represents a linear or branchedsaturated alkyl group having 1 to 4 carbon atoms, a saturated cyclicalkyl group having 3 to 7 carbon atoms, or —(CH₂)_(i)R¹⁴.

Preferred examples of the substituent Xa are oxo group, thioxo group,fluorine atom, chlorine atom, and trifluoromethyl group.

Examples of the linear or branched saturated alkyl group having 1 to 4carbon atoms as the substituent Xa include methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, t-butylgroup, and the like, and among them, methyl group, ethyl group, andpropyl group are particularly preferred.

Further, examples of the saturated cyclic alkyl group having 3 to 7carbon atoms include cyclopropyl group, cyclobutyl group, cyclopentylgroup, cyclohexyl group, cycloheptyl group, and the like.

—(CH₂)_(i)R¹⁴ has the same meaning as defined above. Preferred examplesare 2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group, andN,N-dimethylcarbamoylmethyl group, and a particularly preferred exampleis 2-hydroxyethyl group.

R¹⁰ in —OR¹⁰ represents hydrogen atom, a lower alkyl group having 1 to 4carbon atoms, or a —(CH₂)_(i)R¹⁴ group, and among them, hydrogen atom isa particularly preferred example. Examples of the lower alkyl grouphaving 1 to 4 carbon atoms include methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group, andthe like. Among them, methyl group is particularly preferred.—(CH₂)_(i)R¹⁴ has the same meaning as defined above. Therefore,preferred examples of —OR¹⁰ are hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, and the like, and hydroxylgroup, methoxy group, and 2-hydroxyethyloxy group are particularlypreferred.

R¹¹ in —N(R¹¹)(R¹²) represents hydrogen atom, or a lower alkyl grouphaving 1 to 4 carbon atoms, and R¹² represents hydrogen atom, a loweralkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group having 2 to4 carbon atoms, —COR¹⁵, or —SO₂R¹⁶, or binds to R¹¹ to form a 3- to6-membered ring together with the nitrogen atom to which they bind toform a saturated nitrogen-containing cycloalkyl group or morpholinogroup. R¹⁵ in —COR¹⁵ represents a lower alkyl group having 1 to 4 carbonatoms, a hydroxyalkyl group having 2 to 4 carbon atoms, amino group, amono- or dialkylamino group having 1 to 4 carbon atoms, or -A⁶-Qa. R¹⁶in —SO₂R¹⁶ represents a lower alkyl group having 1 to 4 carbon atoms,amino group, or a mono- or dialkylamino group having 1 to 4 carbonatoms. Specific examples of —N(R¹¹)(R¹²) include amino group,N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,piperidino group, pyrrolidino group, morpholino group,2-hydroxyethylamino group, formylamino group, acetylamino group, benzoylgroup, furan-2-carboxyamino group, 2-hydroxyacetylamino group,2-aminoacetylamino group, carbamoylamino group, N-methylcarbamoylaminogroup, N,N-dimethylcarbamoylamino group, methylsulfonylamino group,sulfamoylamino group, N-methylsulfamoylamino group,N,N-dimethylsulfamoylamino group, and the like. Among them, preferredexamples are amino group, methylamino group, dimethylamino group,2-hydroxyethylamino group, carbamoylamino group, acetylamino group,furan-2-carboxyamino group, 2-hydroxyacetylamino group,2-aminoacetylamino group, methylsulfonylamino group,(N,N-dimethylsulfamoyl)amino group, and the like, and amino group,N-methylamino group, N,N-dimethylamino group, and 2-hydroxyethylaminogroup are particularly preferred.

R¹³ in —SO₂R¹³ represents a lower alkyl group having 1 to 4 carbonatoms, amino group, or a mono- or dialkylamino group having 1 to 4carbon atoms. Preferred examples of —SO₂R¹³ include methanesulfonylgroup, sulfamoyl group, N-methylsulfamoyl group, N,N-dimethylsulfamoylgroup, and the like.

R²⁷ in —COR²⁷ represents hydrogen atom, hydroxyl group, an alkoxy grouphaving 1 to 4 carbon atoms, a lower alkyl group having 1 to 4 carbonatoms, amino group, or a mono- or dialkylamino group having 1 to 4carbon atoms. Specific examples of —COR²⁷ include formyl group, carboxylgroup, methoxycarbonyl group, ethoxycarbonyl group, acetyl group,propionyl group, carbamoyl group, N-methylcarbamoyl group,N,N-dimethylcarbamoyl group, and the like. Carboxyl group, acetyl group,carbamoyl group, N,N-dimethylcarbamoyl group, and the like are preferredexamples, and carboxyl group is particularly preferred.

Preferred examples of the group Xa include oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, N,N-dimethylcarbamoyl group, and the like. Particularly preferredexamples of the group Xa include oxo group, methyl group, ethyl group,propyl group, 2-hydroxyethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, amino group, N-methylamino group,N,N-dimethylamino group, 2-hydroxyethylamino group, carboxyl group, andthe like. Preferred examples of the group Xa which may substitute onnitrogen atom include methyl group, ethyl group, propyl group,hydroxymethyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, and N,N-dimethylcarbamoylmethyl group. Among them,particularly preferred examples are methyl group, ethyl group, propylgroup, and 2-hydroxyethyl group.

Preferred examples of AR substituted with the group Xa or unsubstitutedAR include naphthalen-1-yl group, naphthalen-2-yl group,6-fluoronaphthalen-2-yl group, 6-chloronaphthalen-2-yl group,6-(trifluoromethyl)naphthalen-2-yl group, 5-hydroxynaphthalen-1-ylgroup, 5-hydroxynaphthalen-2-yl group, 6-hydroxynaphthalen-1-yl group,6-hydroxynaphthalen-2-yl group, 7-hydroxynaphthalen-1-yl group,7-hydroxynaphthalen-2-yl group, 5-methoxynaphthalen-1-yl group,5-methoxynaphthalen-2-yl group, 6-methoxynaphthalen-1-yl group,6-methoxynaphthalen-2-yl group, 7-methoxynaphthalen-1-yl group,7-methoxynaphthalen-2-yl group, 5-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-(2-hydroxyethyloxy)naphthalen-2-yl group,7-(2-hydroxyethyloxy)naphthalen-2-yl group,5-(carboxymethyloxy)naphthalen-2-yl group,6-(carboxymethyloxy)naphthalen-2-yl group,7-(carboxymethyloxy)naphthalen-2-yl group,5-(N,N-dimethylcarbamoylmethyloxy)naphthalen-2-yl group,6-(N,N-dimethylcarbamoylmethyloxy)naphthalen-2-yl group,7-(N,N-dimethylcarbamoylmethyloxy)naphthalen-2-yl group,5-aminonaphthalen-1-yl group, 5-aminonaphthalen-2-yl group,6-aminonaphthalen-1-yl group, 6-aminonaphthalen-2-yl group,7-aminonaphthalen-1-yl group, 7-aminonaphthalen-2-yl group,5-(N-methylamino)naphthalen-1-yl group, 5-(N-methylamino)naphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-1-yl group,6-(N-methylamino)naphthalen-2-yl group, 7-(N-methylamino)naphthalen-1-ylgroup, 7-(N-methylamino)naphthalen-2-yl group,5-(N,N-dimethylamino)naphthalen-1-yl group,5-(N,N-dimethylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-1-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,7-(N,N-dimethylamino)naphthalen-1-yl group,7-(N,N-dimethylamino)naphthalen-2-yl group,5-(2-hydroxyethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group,7-(2-hydroxyethylamino)naphthalen-2-yl group,5-acetylaminonaphthalen-2-yl group, 6-acetylaminonaphthalen-2-yl group,6-(2-aminoacetylamino)naphthalen-2-yl group,6-(2-hydroxyacetylamino)naphthalen-2-yl group,7-(2-hydroxyacetylamino)naphthalen-2-yl group,6-[(furan-2-carbonyl)amino]naphthalen-2-yl group,7-[(furan-2-carbonyl)amino]naphthalen-2-yl group,6-[(benzene-2-carbonyl)amino]naphthalen-2-yl group,7-[(benzene-2-carbonyl)amino]naphthalen-2-yl group,6-carbamoylaminonaphthalen-2-yl group,6-methylsulfonylaminonaphthalen-2-yl group,6-sulfamoylaminonaphthalen-2-yl group,6-(N,N-dimethylsulfamoylamino)naphthalen-2-yl group,6-methanesulfonylnaphthalen-2-yl group, 6-sulfamoylnaphthalen-2-ylgroup, 6-(N-methylsulfamoyl)naphthalen-2-yl group,6-(N,N-dimethylsulfamoyl)naphthalen-2-yl group, 6-carboxynaphthalen-2-ylgroup, benzo[b]furan-4-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-4-yl group, 2-methylbenzo[b]furan-5-yl group,3-methylbenzo[b]furan-4-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-4-yl group, 2,3-dimethylbenzo[b]furan-5-ylgroup, 2-carboxybenzo[b]furan-4-yl group, 2-carboxybenzo[b]furan-5-ylgroup, 2-carboxy-3-methylbenzo[b]furan-4-yl group,2-carboxy-3-methylbenzo[b]furan-5-yl group, 3-acetylbenzo[b]furan-4-ylgroup, 3-acetylbenzo[b]furan-5-yl group,3-acetyl-2-methylbenzo[b]furan-4-yl group,3-acetyl-2-methylbenzo[b]furan-5-yl group,3-hydroxymethylbenzo[b]furan-4-yl group,3-hydroxymethylbenzo[b]furan-5-yl group,3-hydroxymethyl-2-methylbenzo[b]furan-4-yl group,3-hydroxymethyl-2-methylbenzo[b]furan-5-yl group, benzo[b]thiophen-4-ylgroup, benzo[b]thiophen-5-yl group, 2-methylbenzo[b]thiophen-4-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-4-ylgroup, 3-methylbenzo[b]thiophen-5-yl group,2,3-dimethylbenzo[b]thiophen-4-yl group,2,3-dimethylbenzo[b]thiophen-5-yl group, 2-carboxybenzo[b]thiophen-4-ylgroup, 2-carboxybenzo[b]thiophen-5-yl group,2-carboxy-3-methylbenzo[b]thiophen-4-yl group,2-carboxy-3-methylbenzo[b]thiophen-5-yl group,3-acetylbenzo[b]thiophen-4-yl group, 3-acetylbenzo[b]thiophen-5-ylgroup, 3-acetyl-2-methylbenzo[b]thiophen-4-yl group,3-acetyl-2-methylbenzo[b]thiophen-5-yl group,3-hydroxymethylbenzo[b]thiophen-4-yl group,3-hydroxymethylbenzo[b]thiophen-5-yl group,3-hydroxymethyl-2-methylbenzo[b]thiophen-4-yl group,3-hydroxymethyl-2-methylbenzo[b]thiophen-5-yl group, 1H-indol-4-ylgroup, 1H-indol-5-yl group, 2-methyl-1H-indol-4-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-4-yl group,3-methyl-1H-indol-5-yl group, 2,3-dimethyl-1H-indol-4-yl group,2,3-dimethyl-1H-indol-5-yl group, 2-carboxy-1H-indol-4-yl group,2-carboxy-1H-indol-5-yl group, 2-carboxy-3-methyl-1H-indol-4-yl group,2-carboxy-3-methyl-1H-indol-5-yl group, 3-acetyl-1H-indol-4-yl group,3-acetyl-1H-indol-5-yl group, 3-acetyl-2-methyl-1H-indol-4-yl group,3-acetyl-2-methyl-1H-indol-5-yl group, 3-hydroxymethyl-1H-indol-4-ylgroup, 3-hydroxymethyl-1H-indol-5-yl group,3-hydroxymethyl-2-methyl-1H-indol-4-yl group,3-hydroxymethyl-2-methyl-1H-indol-5-yl group, 1-methyl-1H-indol-4-ylgroup, 1-methyl-1H-indol-5-yl group, 1,2-dimethyl-1H-indol-4-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-4-yl group,1,3-dimethyl-1H-indol-5-yl group, 1,2,3-trimethyl-1H-indol-4-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 2-carboxy-1-methyl-1H-indol-4-ylgroup, 2-carboxy-1-methyl-1H-indol-5-yl group,2-carboxy-1,3-dimethyl-1H-indol-4-yl group,2-carboxy-1,3-dimethyl-1H-indol-5-yl group,3-acetyl-1-methyl-1H-indol-4-yl group, 3-acetyl-1-methyl-1H-indol-5-ylgroup, 3-acetyl-1,2-dimethyl-1H-indol-4-yl group,3-acetyl-1,2-dimethyl-1H-indol-5-yl group,3-hydroxymethyl-1-methyl-1H-indol-4-yl group,3-hydroxymethyl-1-methyl-1H-indol-5-yl group,3-hydroxymethyl-1,2-dimethyl-1H-indol-4-yl group,3-hydroxymethyl-1,2-dimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-4-ylgroup, 1-ethyl-1H-indol-5-yl group, 1-ethyl-2-methyl-1H-indol-4-ylgroup, 1-ethyl-2-methyl-1H-indol-5-yl group,1-ethyl-3-methyl-1H-indol-4-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-4-yl group,1-ethyl-2,3-dimethyl-1H-indol-5-yl group,2-carboxy-1-ethyl-1H-indol-4-yl group, 2-carboxy-1-ethyl-1H-indol-5-ylgroup, 2-carboxy-1-ethyl-3-methyl-1H-indol-4-yl group,2-carboxy-1-ethyl-3-methyl-1H-indol-5-yl group,3-acetyl-1-ethyl-1H-indol-4-yl group, 3-acetyl-1-ethyl-1H-indol-5-ylgroup, 3-acetyl-1-ethyl-2-methyl-1H-indol-4-yl group,3-acetyl-1-ethyl-2-methyl-1H-indol-5-yl group,1-ethyl-3-hydroxymethyl-1H-indol-4-yl group,1-ethyl-3-hydroxymethyl-1H-indol-5-yl group,1-ethyl-3-hydroxymethyl-2-methyl-1H-indol-4-yl group,1-ethyl-3-hydroxymethyl-2-methyl-1H-indol-5-yl group,1-propyl-1H-indol-4-yl group, 1-propyl-1H-indol-5-yl group,2-methyl-1-propyl-1H-indol-4-yl group, 2-methyl-1-propyl-1H-indol-5-ylgroup, 3-methyl-1-propyl-1H-indol-4-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-4-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,2-carboxy-1-propyl-1H-indol-4-yl group, 2-carboxy-1-propyl-1H-indol-5-ylgroup, 2-carboxy-3-methyl-1-propyl-1H-indol-4-yl group,2-carboxy-3-methyl-1-propyl-1H-indol-5-yl group,3-acetyl-1-propyl-1H-indol-4-yl group, 3-acetyl-1-propyl-1H-indol-5-ylgroup, 3-acetyl-2-methyl-1-propyl-1H-indol-4-yl group,3-acetyl-2-methyl-1-propyl-1H-indol-5-yl group,3-hydroxymethyl-1-propyl-1H-indol-4-yl group,3-hydroxymethyl-1-propyl-1H-indol-5-yl group,3-hydroxymethyl-2-methyl-1-propyl-1H-indol-4-yl group,3-hydroxymethyl-2-methyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-4-yl group, 1-(2-hydroxyethyl)-1H-indol-5-ylgroup, 1-(2-hydroxyethyl)-2-methyl-1H-indol-4-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-4-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-4-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group,2-carboxy-1-(2-hydroxyethyl)-1H-indol-4-yl group,2-carboxy-1-(2-hydroxyethyl)-1H-indol-5-yl group,2-carboxy-1-(2-hydroxyethyl)-3-methyl-1H-indol-4-yl group,2-carboxy-1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,3-acetyl-1-(2-hydroxyethyl)-1H-indol-4-yl group,3-acetyl-1-(2-hydroxyethyl)-1H-indol-5-yl group,3-acetyl-1-(2-hydroxyethyl)-2-methyl-1H-indol-4-yl group,3-acetyl-1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-hydroxymethyl-1H-indol-4-yl group,1-(2-hydroxyethyl)-3-hydroxymethyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-hydroxymethyl-2-methyl-1H-indol-4-yl group,1-(2-hydroxyethyl)-3-hydroxymethyl-2-methyl-1H-indol-5-yl group,1-carboxymethyl-1H-indol-4-yl group, 1-carboxymethyl-1H-indol-5-ylgroup, 1-carboxymethyl-2-methyl-1H-indol-4-yl group,1-carboxymethyl-2-methyl-1H-indol-5-yl group,1-carboxymethyl-3-methyl-1H-indol-4-yl group,1-carboxymethyl-3-methyl-1H-indol-5-yl group,1-carboxymethyl-2,3-dimethyl-1H-indol-4-yl group,1-carboxymethyl-2,3-dimethyl-1H-indol-5-yl group,2-carboxy-1-carboxymethyl-1H-indol-4-yl group,2-carboxy-1-carboxymethyl-1H-indol-5-yl group,2-carboxy-1-carboxymethyl-3-methyl-1H-indol-4-yl group,2-carboxy-1-carboxymethyl-3-methyl-1H-indol-5-yl group,3-acetyl-1-carboxymethyl-1H-indol-4-yl group,3-acetyl-1-carboxymethyl-1H-indol-5-yl group,3-acetyl-1-carboxymethyl-2-methyl-1H-indol-4-yl group,3-acetyl-1-carboxymethyl-2-methyl-1H-indol-5-yl group,1-carboxymethyl-3-hydroxymethyl-1H-indol-4-yl group,1-carboxymethyl-3-hydroxymethyl-1H-indol-5-yl group,1-carboxymethyl-3-hydroxymethyl-2-methyl-1H-indol-4-yl group,1-carboxymethyl-3-hydroxymethyl-2-methyl-1H-indol-5-yl group,benzothiazol-6-yl group, 2-methylbenzothiazol-6-yl group,2-methoxybenzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group,2-(N-methylamino)benzothiazol-6-yl group,2-(N,N-dimethylamino)benzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, 2-methylquinolin-3-yl group, quinolin-6-yl group,2-methylquinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 3-methylbenzo[d]isothiazol-5-yl group,1H-indazol-5-yl group, 3-methyl-1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1,3-dimethyl-1H-indazol-5-yl group,1-ethyl-1H-indazol-5-yl group, 1-ethyl-3-methyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 3-methyl-1-propyl-1H-indazol-5-yl group,1-(2-hydroxyethyl)-1H-indazol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indazol-5-yl group,1-(carboxymethyl)-1H-indazol-5-yl group,1-(carboxymethyl)-3-methyl-1H-indazol-5-yl group,3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-ylgroup, 1-ethyl-3-hydroxy-1H-indazol-5-yl group, benzo[c]isothiazol-5-ylgroup, 3-methylbenzo[c]isothiazol-5-yl group, 2-methyl-2H-indazol-5-ylgroup, 2,3-dimethyl-2H-indazol-5-yl group, 2-ethyl-2H-indazol-5-ylgroup, 2-ethyl-3-methyl-2H-indazol-5-yl group, 2-propyl-2H-indazol-5-ylgroup, 3-methyl-2-propyl-2H-indazol-5-yl group,2-(2-hydroxyethyl)-2H-indazol-5-yl group,2-(2-hydroxyethyl)-3-methyl-2H-indazol-5-yl group,2-(carboxymethyl)-2H-indazol-5-yl group,2-(carboxymethyl)-3-methyl-2H-indazol-5-yl group,imidazo[1,2-a]pyridin-6-yl group, 2-methyl-imidazo[1,2-a]pyridin-6-ylgroup, 3-methyl-imidazo[1,2-a]pyridin-6-yl group,2,3-dimethyl-imidazo[1,2-a]pyridin-6-yl group,1H-pyrrolo[2,3-b]pyridin-5-yl group,2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1,2-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,2,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1,2,3-trimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-2,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,2-methyl-1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,3-methyl-1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,2,3-dimethyl-1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(carboxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(carboxymethyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(carboxymethyl)-3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(carboxymethyl)-2,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,isoquinolin-6-yl group, 1-methylisoquinolin-6-yl group,1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group,cinnolin-5-yl group, quinazolin-6-yl group, quinazolin-7-yl group,quinazolin-5-yl group, 2-methylquinazolin-6-yl group, quinoxalin-6-ylgroup, quinoxalin-5-yl group, 2-methylquinoxalin-6-yl group,1H-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group,1-methyl-1H-benzimidazol-5-yl group, 2-methyl-1H-benzimidazol-5-ylgroup, 1,2-dimethyl-1H-benzimidazol-5-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,2-methylbenzoxazol-5-yl group, 1H-pyrrolo[3,2-b]pyridin-5-yl group,1H-pyrrolo[3,2-b]pyridin-6-yl group,1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[3,2-b]pyridin-5-yl group,2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl group,3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl group,1,3-dimethyl-1H-pyrrolo[3,2-b]pyridin-5-yl group,benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-yl group,1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1-methyl-1H-benzotriazol-5-yl group, 1-ethyl-1H-benzotriazol-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-2-on-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-2-on-4-yl group,1-methyl-1,3-dihydropyrrolo[2,3-b]pyridin-2-on-5-yl group,1,3-dihydrobenzimidazol-2-on-5-yl group,1,3-dihydrobenzimidazol-2-on-4-yl group,1-methyl-1,3-dihydrobenzimidazol-2-on-5-yl group,1,3-dihydrobenzimidazole-2-thion-5-yl group,1,3-dihydrobenzimidazole-2-thion-4-yl group,1-methyl-1,3-dihydrobenzimidazole-2-thion-5-yl group,3H-benzoxazol-2-on-6-yl group, 3H-benzoxazol-2-on-7-yl group,3H-benzoxazol-2-on-5-yl group, 3H-benzoxazol-2-on-4-yl group,3-methyl-3H-benzoxazol-2-on-6-yl group, 3H-benzoxazole-2-thion-6-ylgroup, 3H-benzoxazole-2-thion-7-yl group, 3H-benzoxazole-2-thion-5-ylgroup, 3H-benzoxazole-2-thion-4-yl group,3-methyl-3H-benzoxazole-2-thion-6-yl group, phthalazin-6-yl group,phthalazin-5-yl group, [1,8]naphthalidin-3-yl group,[1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group,1-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl group,1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl group,2-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl group,3-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl group,1,3-dimethyl-1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[2,3-c]pyridin-5-yl group, 1H-pyrrolo[2,3-c]pyridin-4-ylgroup, 1-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-c]pyridin-5-yl group,2-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl group,3-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl group,1,3-dimethyl-1H-pyrrolo[2,3-c]pyridin-5-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl group,1-ethyl-1H-pyrazolo[4,3-b]pyridin-5-yl group,3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl group,1,3-dimethyl-1H-pyrazolo[4,3-b]pyridin-5-yl group,1H-pyrazolo[4,3-c]pyridin-6-yl group, 1H-pyrazolo[4,3-c]pyridin-4-ylgroup, 1-methyl-1H-pyrazolo[4,3-c]pyridin-6-yl group,1-ethyl-1H-pyrazolo[4,3-c]pyridin-6-yl group,3-methyl-1H-pyrazolo[4,3-c]pyridin-6-yl group,1,3-dimethyl-1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[3,4-c]pyridin-5-yl group, 1H-pyrazolo[3,4-c]pyridin-4-ylgroup, 1-methyl-1H-pyrazolo[3,4-c]pyridin-5-yl group,1-ethyl-1H-pyrazolo[3,4-c]pyridin-5-yl group,3-methyl-1H-pyrazolo[3,4-c]pyridin-5-yl group,1,3-dimethyl-1H-pyrazolo[3,4-c]pyridin-5-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, 1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl group,1-ethyl-1H-pyrazolo[3,4-b]pyridin-5-yl group,3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl group,1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-5-yl group,[1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group,3-methyl[1,2,4]triazolo[4,3-a]pyridin-6-yl group,thieno[3,2-c]pyridin-2-yl group, thieno[3,2-c]pyridin-3-yl group,thieno[3,2-c]pyridin-6-yl group, 2-methylthieno[3,2-c]pyridin-2-ylgroup, 3-methylthieno[3,2-c]pyridin-2-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,2-methylthieno[3,2-b]pyridin-2-yl group,3-methylthieno[3,2-b]pyridin-2-yl group, 1H-thieno[3,2-c]pyrazol-5-ylgroup, 1H-thieno[3,2-c]pyrazol-4-yl group,1-methyl-1H-thieno[3,2-c]pyrazol-5-yl group,1-ethyl-1H-thieno[3,2-c]pyrazol-5-yl group,3-methyl-1H-thieno[3,2-c]pyrazol-5-yl group,1,3-dimethyl-1H-thieno[3,2-c]pyrazol-5-yl group, benzo[d]isoxazol-5-ylgroup, benzo[d]isoxazol-4-yl group, benzo[d]isoxazol-6-yl group,benzo[d]isoxazol-7-yl group, 3-methylbenzo[d]isoxazol-5-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group,3-methylbenzo[c]isoxazol-5-yl group, indolizin-7-yl group,indolizin-6-yl group, indolizine-8-yl group, 1,3-dihydroindol-2-on-5-ylgroup, 1,3-dihydroindol-2-on-4-yl group, 1,3-dihydroindol-2-on-6-ylgroup, 1-methyl-1,3-dihydro-indol-2-on-5-yl group,1H-pyrazolo[3,4-d]thiazol-5-yl group, 2H-isoindol-5-yl group,2H-isoindol-4-yl group, 2-methyl-2H-isoindol-5-yl group, 4H-chromen-6-ylgroup, 4H-chromen-5-yl group, chromen-4-on-7-yl group, chromen-4-on-6-ylgroup, and the like.

Particularly preferred examples include naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group,benzoxazol-5-yl group, and the like.

Particularly preferred examples include naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-aminonaphthalen-2-yl group, 6-(N,N-dimethylamino)naphthalen-2-ylgroup, benzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-ylgroup, benzothiazol-6-yl group, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-yl group,quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,3-hydroxy-1H-indazol-5-yl group, 3-hydroxy-1-methyl-1H-indazol-5-ylgroup, 1-ethyl-3-hydroxy-1H-indazol-5-yl group,imidazo[1,2-a]pyridin-6-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-yl group,1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group,benzoxazol-5-yl group, and the like.

In the formula (I), the group Y is defined to be hydrogen atom, a loweralkyl group having 1 to 4 carbon atoms, —(CH₂)_(m)N(R¹⁸)(R¹⁹), or—C(R²⁰)₂OC(O)A³R²′, and among them, hydrogen atom is particularlypreferred.

Examples of the lower alkyl group having 1 to 4 carbon atoms includemethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, t-butyl group, and the like. Among them, methyl group,and ethyl group are particularly preferred.

Symbol m in —(CH₂)_(m)N(R¹⁸)(R¹⁹) is defined to be an integer of 2 or 3.R¹⁸ is the same as R¹⁹, or binds to R¹⁹ to represent a saturatednitrogen-containing cycloalkyl group forming a 3- to 6-membered ringtogether with nitrogen atom, or form morpholino group together withnitrogen atom, and R¹⁹ is defined to be methyl group, ethyl group, orpropyl group. Examples of —(CH₂)_(m)N(R¹⁸)(R¹⁹) include2-(N,N-dimethylamino)ethyl group, 2-(N,N-diethylamino)ethyl group,2-(N,N-dipropylamino)ethyl group, 3-(N,N-dimethylamino)propyl group,3-(N,N-diethylamino)propyl group, 2-(N,N-dipropylamino)propyl group,2-pyrrolidin-1-ylethyl group, 2-piperidin-1-ylethyl group,2-morpholin-4-ylethyl group, 3-pyrrolidin-1-ylpropyl group,3-piperidin-1-ylpropyl group, 3-morpholin-4-ylpropyl group, and thelike.

R²⁰ in —C(R²⁰)₂OC(O)A³R²¹ is defined to be hydrogen atom, methyl group,ethyl group, or propyl group. R²¹ is defined to be a lower alkyl grouphaving 1 to 4 carbon atoms, a cyclic saturated alkyl group having 3 to 6carbon atoms group, or phenyl group. Examples of the lower alkyl grouphaving 1 to 4 carbon atoms include methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group, andthe like, and examples of the cyclic saturated alkyl group having 3 to 6carbon atoms group include cyclopropyl group, cyclobutyl group,cyclopentyl group, and cyclohexyl group. A³ is defined to be a singlebond, or oxygen atom. Examples of —C(R²⁰)₂OC(O)A³R²¹ includeacetoxymethyl group, propionyloxymethyl group, butyryloxymethyl group,(2-methylpropionyl)oxymethyl group, (2,2-dimethylpropionyl)oxymethylgroup, cyclopropionyloxymethyl group, cyclopentanoyloxymethyl group,cyclohexanoyloxymethyl group, phenylcarboxymethyl group,1-acetoxy-1-methylethyl group, 1-methyl-1-(2-methylpropionyloxy)ethylgroup, 1-cyclopentanoyloxy-1-methylethyl group,1-cyclohexanoyloxy-1-methylethyl group, methoxycarbonyloxymethyl group,ethoxycarbonyloxymethyl group, isopropyloxycarbonyloxymethyl group,t-butyloxycarbonyloxymethyl group, cyclopropyloxycarbonyloxymethylgroup, cyclopentyloxycarbonyloxymethyl group,cyclohexyloxycarbonyloxymethyl group, phenyloxycarbonyloxymethyl group,1-methoxycarbonyloxy-1-methylethyl group,1-ethoxycarbonyloxy-1-methylethyl group,1-isopropyloxycarbonyloxy-1-methylethyl group,1-t-butyloxycarbonyloxy-1-methylethyl group,1-cyclopropyloxycarbonyloxy-1-methylethyl group,1-cyclopentyloxycarbonyloxy-1 methylethyl group,1-cyclohexyloxycarbonyloxy-1-methylethyl group,1-methyl-1-phenyloxycarbonyloxyethyl group, and the like.

In a preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 1 to 3.

AR binds to C², Rs binds to any of the atoms C³, C⁴ and C⁵, and aring-constituting carbon atom to which Rs does not bind among C³, C⁴,and C⁵ may be replaced with V.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as any one of fluorine atom, chlorine atom, bromineatom, nitro group, methyl group, hydroxyl group, methoxy group, aminogroup, N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group.

Rs represents -D-Rx, or —N(Ry)(Rz). D represents oxygen atom, or sulfuratom. Rx represents butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rbrepresents a group as any one of phenyl group, thienyl group, furylgroup, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthylgroup, indanyl group, indolyl group, and dihydrobenzodioxyl group. A²represents a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² represents oxygen atom, sulfur atom,—N(methyl), or —N(ethyl)-, A¹ represents ethylene). R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q represents phenyl group, A¹ represents a single bond, orunsubstituted methylene, and A² represents a single bond, one of R² andR³ represents a substituent other than hydrogen atom). Symbol p in Rcrepresents an integer of 2 or 3, and A⁴ represents a single bond ormethylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, or a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Rerepresents a group as any one of methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group,cyclopropyl group, cyclopentyl group, cyclohexyl group,cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethylgroup, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-ylgroup, methoxy group, ethoxy group, propyloxy group, isopropyloxy group,butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxygroup, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxygroup, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxygroup, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxygroup, amino group, N-methylamino group, N,N-dimethylamino group,N-ethylamino group, N,N-diethylamino group, N-propylamino group,N-isopropylamino group, N-butylamino group, N-isobutylamino group,N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylaminogroup, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,and ethyloxycarbonylamino group.

Rz represents a group as any one of butyl group, isobutyl group,2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenylgroup, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz to form pyrrolidino group, piperidinogroup, piperazino group, morpholino group, pyrrol-1-yl group,imidazol-1-yl group, or pyrazol-1-yl group together with nitrogen atom.

AR represents naphthalen-2-yl group, naphthalen-1-yl group,benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol 5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (these groups may be substituted with one of Xa or two or more ofthe same or different Xa). The substituent Xa represents a group as anyone of oxo group, thioxo group, fluorine atom, chlorine atom,trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 1 to 3.

AR binds to C³, Rs binds to any of the atoms C⁴, C⁵, and C⁶, and aring-constituting carbon atom to which Rs does not bind among C⁴, C⁵,and C⁶ may be replaced with V.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as any one of fluorine atom, chlorine atom, bromineatom, nitro group, methyl group, hydroxyl group, methoxy group, aminogroup, N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group.

Rs represents -D-Rx, or —N(Ry)(Rz). D represents oxygen atom, or sulfuratom. Rx represents butyl group, isobutyl group, 2-ethylbutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or represents Rb, or Rc. Q in Rbrepresents a group as any one of phenyl group, thienyl group, furylgroup, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthylgroup, indanyl group, indolyl group, and dihydrobenzodioxyl group. A²represents a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² represents oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ represents ethylene). R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q represents phenyl group, A¹ represents a single bond, orunsubstituted methylene, and A² represents a single bond, one of R² andR³ represents a substituent other than hydrogen atom). Symbol p in Rcrepresents an integer of 2 or 3, and A⁴ represents a single bond ormethylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, or a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Rerepresents a group as any one of methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group,cyclopropyl group, cyclopentyl group, cyclohexyl group,cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethylgroup, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-ylgroup, methoxy group, ethoxy group, propyloxy group, isopropyloxy group,butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxygroup, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxygroup, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxygroup, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxygroup, amino group, N-methylamino group, N,N-dimethylamino group,N-ethylamino group, N,N-diethylamino group, N-propylamino group,N-isopropylamino group, N-butylamino group, N-isobutylamino group,N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylaminogroup, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,and ethyloxycarbonylamino group. Rz represents a group as any of butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethylgroup, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz to form pyrrolidino group, piperidinogroup, piperazino group, morpholino group, pyrrol-1-yl group,imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogenatom to which they binds.

AR represents naphthalen-2-yl group, naphthalen-1-yl group,benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa). The substituent Xa representsa group as any one of oxo group, thioxo group, fluorine atom, chlorineatom, trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In a preferred embodiment of the present invention, a compound or a saltthereof satisfying all of the following requirements is excluded fromthe compound represented by the formula (I) or a salt thereof.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 1 to 3.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ represents a ring-constituting carbon atom whichmay be substituted with Zx, and C² and C⁶ represent unsubstitutedring-constituting carbon atom.

Zx represents fluorine atom, chlorine atom, nitro group, amino group,methyl group, or a OR⁹ group, and R⁹ represents hydrogen atom or a loweralkyl group having 1 to 4 carbon atoms.

Rs represents —O-Rx. Rx represents a linear or branched saturated alkylgroup having 3 to 8 carbon atoms, or represents Ra or Rb, Q in Rbrepresents a residue of a partially unsaturated or completelyunsaturated monocyclic or condensed bicyclic carbon ring or heterocyclicring (q), and binds to A² at an arbitrary position on the ring. Theheterocyclic ring (q) contains one or two of the same or differentring-constituting heteroatoms selected from the group consisting ofnitrogen atom, oxygen atom, and sulfur atom.

AR represents a residue of naphthalene, benzofuran, benzo[b]thiophene,indole, benzothiazole, dihydro-3H-benzothiazole, quinoline,dihydro-1H-quinoline, benzo[d]isothiazole, 1H-indazole,benzo[c]isothiazole, 2H-indazole, imidazo[1,2-a]pyridine,1H-pyrrolo[2,3-b]pyridine, isoquinoline, or dihydro-2H-isoquinoline (theaforementioned residue may be substituted with one of Xa or two or moreof the same or different Xa).

In another preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 1 to 3.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ may be replaced with V, and C² and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as any one of fluorine atom, chlorine atom, bromineatom, nitro group, methyl group, hydroxyl group, methoxy group, aminogroup, N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group.

Rs represents —O-Rx. Rx represents butyl group, isobutyl group,2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, cyclopentylmethyl group, cyclohexylmethyl group,2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rbor Rc. Q in Rb represents a group as any one of phenyl group, thienylgroup, furyl group, pyridyl group, oxazolyl group, naphthyl group,tetrahydronaphthyl group, indanyl group, indolyl group, anddihydrobenzodioxyl group. A² represents a single bond, oxygen atom,sulfur atom, —N(methyl)-, or —N(ethyl)- (provided that when A²represents oxygen atom, sulfur atom, —N(methyl)-, or —N(ethyl)-, A¹represents ethylene). R² and R³ independently represent hydrogen atom,methyl group, fluorine atom, chlorine atom, trifluoromethyl group,methoxy group, dimethylamino group, acetylamino group, ormethylsulfonylamino group (provided that when Q represents phenyl group,A¹ represents a single bond, or unsubstituted methylene, and A²represents a single bond, one of R² and R³ represents a substituentother than hydrogen atom). Symbol p in Rc represents an integer of 2 or3, and A⁴ represents a single bond or methylene. A⁵ represents —C(O)—,—C(S)—, or —S(O)₂—. Rd represents hydrogen atom, or a group as any oneof methyl group, ethyl group, propyl group, isopropyl group, butylgroup, isobutyl group, cyclopropyl group, cyclopropylmethyl group,cyclopentyl group, cyclopentylmethyl group, cyclohexyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, and pyridin-4-yl group. Re represents a groupas any one of methyl group, ethyl group, propyl group, isopropyl group,butyl group, isobutyl group, t-butyl group, cyclopropyl group,cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, andethyloxycarbonylamino group.

AR represents any one of cinnolin-6-yl group, cinnolin-5-yl group,quinazolin-6-yl group, quinazolin-7-yl group, quinazolin-5-yl group,quinoxalin-2-yl group, quinoxalin-6-yl group, quinoxalin-5-yl group,1H-benzimidazol-5-yl group, 1H-benzimidazol-4-yl group, benzoxazol-5-ylgroup, benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-ylgroup, 1H-pyrrolo[3,2-b]pyridin-5-yl group,1H-pyrrolo[3,2-b]pyridin-6-yl group, benzo[1,2,5]thiadiazol-5-yl group,benzo[1,2,5]thiadiazol-4-yl group, 1H-benzotriazol-5-yl group,1H-benzotriazol-4-yl group, 1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, and 4H-chromen-5-ylgroup (these groups may be substituted with one of Xa or two or more ofthe same or different Xa). The substituent Xa represents a group as anyone of oxo group, thioxo group, fluorine atom, chlorine atom,trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 1 to 3.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ may be replaced with V, and C² and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as any one of, chlorine atom, bromine atom, nitrogroup, methyl group, hydroxyl group, methoxy group, amino group,N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group.

Rs represents —S-Rx. Rx represents butyl group, isobutyl group,2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, cyclopentylmethyl group, cyclohexylmethyl group,2-cyclopentylethyl group, or 2-cyclohexylethyl group, or represents Rbor Rc. Q in Rb represents a group as any one of phenyl group, thienylgroup, furyl group, pyridyl group, oxazolyl group, naphthyl group,tetrahydronaphthyl group, indanyl group, indolyl group, anddihydrobenzodioxyl group. A² represents a single bond, oxygen atom,sulfur atom, —N(methyl), or —N(ethyl)- (provided that when A² representsoxygen atom, sulfur atom, —N(methyl)-, or —N(ethyl)-, A¹ representsethylene). R² and R³ independently represent hydrogen atom, methylgroup, fluorine atom, chlorine atom, trifluoromethyl group, methoxygroup, dimethylamino group, acetylamino group, or methylsulfonylaminogroup (provided that when Q represents phenyl group, A¹ represents asingle bond, or unsubstituted methylene, and A² represents a singlebond, one of R² and R³ represents a substituent other than hydrogenatom). Symbol p in Rc represents an integer of 2 or 3, and A⁴ representsa single bond or methylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rdrepresents hydrogen atom, or a group as any one of methyl group, ethylgroup, propyl group, isopropyl group, butyl group, isobutyl group,cyclopropyl group, cyclopropylmethyl group, cyclopentyl group,cyclopentylmethyl group, cyclohexyl group, cyclohexylmethyl group,phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenylgroup, benzyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethylgroup, pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group.Re represents a group as any one of methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group,cyclopropyl group, cyclopentyl group, cyclohexyl group,cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethylgroup, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,methoxy group, ethoxy group, propyloxy group, isopropyloxy group,butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxygroup, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxygroup, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxygroup, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxygroup, amino group, N-methylamino group, N,N-dimethylamino group,N-ethylamino group, N,N-diethylamino group, N-propylamino group,N-isopropylamino group, N-butylamino group, N-isobutylamino group,N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylaminogroup, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,and ethyloxycarbonylamino group.

AR represents naphthalen-2-yl group, naphthalen-1-yl group,benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (these groups may be substituted with one of Xa or two or more ofthe same or different Xa). The substituent Xa represents a group as anyone of oxo group, thioxo group, fluorine atom, chlorine atom,trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 1 to 3.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, and C², C⁵ and C⁶ represent unsubstitutedring-constituting carbon atom.

Rs represents —N(Ry)(Rz). Rz represents a group as any one of butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethylgroup, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz to form pyrrolidino group, piperidinogroup, piperazino group, morpholino group, pyrrol-1-yl group,imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogenatom to which they bind.

AR represents naphthalen-2-yl group, naphthalen-1-yl group,benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (these groups may be substituted with one of Xa or two or more ofthe same or different Xa). The substituent Xa represents a group as anyone of oxo group, thioxo group, fluorine atom, chlorine atom,trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 1 to 3.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ may be replaced with V, and C² and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as any one of chlorine atom, bromine atom, nitrogroup, methyl group, hydroxyl group, methoxy group, amino group,N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group.

Rs represents -D-Rc, and D represents oxygen atom or sulfur atom. Symbolp in Rc represents an integer of 2 or 3, and A⁴ represents a single bondor methylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, or a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group., cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Rerepresents a group as any one of methyl group, ethyl group, propylgroup, isopropyl group, butyl group, isobutyl group, t-butyl group,cyclopropyl group, cyclopentyl group, cyclohexyl group,cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,phenylmethyl group, 4-chlorophenylmethyl group, 4-fluorophenylmethylgroup, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-ylgroup, methoxy group, ethoxy group, propyloxy group, isopropyloxy group,butyloxy group, isobutyloxy group, t-butyloxy group, cyclopropyloxygroup, cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxygroup, cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxygroup, 4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxygroup, amino group, N-methylamino group, N,N-dimethylamino group,N-ethylamino group, N,N-diethylamino group, N-propylamino group,N-isopropylamino group, N-butylamino group, N-isobutylamino group,N-t-butylamino group, N-cyclopropylamino group, N-cyclopentylaminogroup, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,and ethyloxycarbonylamino group.

AR represents naphthalen-2-yl group, naphthalen-1-yl group,benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (these groups may be substituted with one of Xa or two or more ofthe same or different Xa). The substituent Xa represents a group as anyone of oxo group, thioxo group, fluorine atom, chlorine atom,trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link is —(CH₂)_(n)—, n is an integer of 1 to 3, C³ is carbon atom boundwith AR, C⁴ is carbon atom bound with R⁵, C⁵ may be replaced with V, C²and C⁶ are unsubstituted ring-constituting carbon atoms,

V is nitrogen atom or V is carbon atom substituted with Zx, Zx is anyone of fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group,

Rs is -D-Rx, D is a single bond, Rx is butyl group, isobutyl group,2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, cyclopentylmethyl group, cyclohexylmethyl group,2-cyclopentylethyl group, or 2-cyclohexylethyl group, or Rx is Rb or Rc(provided that Q in Rb is phenyl group, thienyl group, furyl group,pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthyl group,indanyl group, indolyl group, or dihydrobenzodioxyl group), A² is asingle bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)-(provided that when A² represents oxygen atom, sulfur atom,—N(methyl)- or —N(ethyl)-, A¹ represents ethylene), R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group, p in Rc is aninteger of 2 or 3, A⁴ is a single bond or methylene, A⁵ is —C(O)—,—C(S)—, or —S(O)₂—, Rd is hydrogen atom, or methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, or pyridin-4-yl group, Re ismethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, t-butyl group, cyclopropyl group, cyclopentyl group,cyclohexyl group, cyclopentylmethyl group, cyclohexylmethyl group,phenyl group, 4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenylgroup, phenylmethyl group, 4-chlorophenylmethyl group,4-fluorophenylmethyl group, pyridin-2-yl group, pyridin-3-yl group,pyridin-4-yl group, methoxy group, ethoxy group, propyloxy group,isopropyloxy group, butyloxy group, isobutyloxy group, t-butyloxy group,cyclopropyloxy group, cyclopentyloxy group, cyclohexyloxy group,cyclopentylmethyloxy group, cyclohexylmethyloxy group, phenyloxy group,4-methylphenyloxy group, 4-chlorophenyloxy group, 4-fluorophenyloxygroup, thiomethoxy group, amino group, N-methylamino group,N,N-dimethylamino group, N-ethylamino group, N,N-diethylamino group,N-propylamino group, N-isopropylamino group, N-butylamino group,N-isobutylamino group, N-t-butylamino group, N-cyclopropylamino group,N-cyclopentylamino group, N-cyclohexylamino group, N-phenylamino group,N-(4-methylphenyl)amino group, N-(4-chlorophenyl)amino group,N-(4-fluorophenyl)amino group, N-(pyridin-2-yl)amino group,N-(pyridin-3-yl)amino group, N-(pyridin-4-yl)amino group,N-(furan-2-yl)amino group, N-(furan-3-yl)amino group,N-(thiophen-2-yl)amino group, N-(thiophen-3-yl)amino group, pyrrolidinogroup, piperidino group, morpholino group, methyloxycarbonylamino group,or ethyloxycarbonylamino group,

AR is naphthalen-2-yl group, naphthalen-1-yl group, benzofuran-5-ylgroup, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa), Xa is oxo group, thioxo group,fluorine atom, chlorine atom, trifluoromethyl group, methyl group, ethylgroup, propyl group, 2-hydroxyethyl group, carboxymethyl group,2-carboxyethyl group, N,N-dimethylcarbamoylmethyl group, hydroxyl group,methoxy group, 2-hydroxyethyloxy group, carboxymethyloxy group,2-carboxyethyloxy group, N,N-dimethylcarbamoylmethyloxy group, aminogroup, methylamino group, dimethylamino group, 2-hydroxyethylaminogroup, carbamoylamino group, acetylamino group, furan-2-carboxyaminogroup, 2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, or N,N-dimethylcarbamoyl group, and

Y is hydrogen atom, methyl group, or ethyl group.

In a particularly preferred embodiment of the present invention, thecompound represented by the formula (I) or a salt thereof satisfies allof the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C² represents carbon atom to which AR bonds, C³ represents carbon atomto which Rs bonds, C⁴ may be replaced with V, and C⁵ and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as any one of fluorine atom, methyl group, hydroxylgroup, amino group, N-methylamino group, and N,N-dimethylamino group.

Rs represents —O-Rx. Rx represents a group as any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n), symbol n represents an integer of 2.

C² represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ may be replaced with V, and C³ and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as, any one of fluorine atom, methyl group, hydroxylgroup, amino group, N-methylamino group, and N,N-dimethylamino group.

Rs represents —O-Rx. Rx represents a group as any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁵ represents carbon atomto which Rs bonds, and C², C⁴ and C⁶ represent unsubstitutedring-constituting carbon atom.

Rs represents —O-Rx. Rx represents a group as any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ represents nitrogen atom, and C² and C⁶ representunsubstituted ring-constituting carbon atom.

Rs represents —O-Rx. Rx represents a group as any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another preferred embodiment of the present invention, the compoundrepresented by the formula (I) or a salt thereof satisfies all of thefollowing requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁶ represents carbon atom substituted with Zx, and C²and C⁵ represent unsubstituted ring-constituting carbon atom.

Zx represents fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group.

Rs represents —O-Rx. Rx represents a group as any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, and C², C⁵ and C⁶ represent unsubstitutedring-constituting carbon atom.

Rs represents —N(Ry)(Rz). Rz represents a group as any one of butylgroup, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexylgroup, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethylgroup, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz to form pyrrolidino group, piperidinogroup, or morpholino group together with nitrogen atom to which theybonds.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, and C², C⁵ and C⁶ represent unsubstitutedring-constituting carbon atom.

Rs represents —N(Ry)(Rz). —N(Ry)(Rz) is any one of N,N-dimethylaminogroup, N-ethyl-N-methylamino group, N,N-diethylamino group,N-methyl-N-propylamino group, N-ethyl-N-propylamino group,N-isopropyl-N-methylamino group, N-ethyl-N-isopropylamino group,N-butylamino group, N-butyl-N-methylamino group, N-butyl-N-ethylaminogroup, N-isobutylamino group, N-isobutyl-N-methylamino group,N-ethyl-N-isobutylamino group, N-(2-ethylbutyl)amino group,N-(2-ethylbutyl)-N-methylamino group, N-cyclopentylamino group,N-cyclopentyl-N-methylamino group, N-cyclohexylamino group,N-cyclohexyl-N-methylamino group, N-cycloheptylamino group,N-(cyclopentylmethyl)amino group, N-(cyclopentylmethyl)-N-methylaminogroup, N-(cyclohexylmethyl)amino group,N-(cyclohexylmethyl)-N-methylamino group, N-(2-methylphenyl)amino group,N-(4-methylphenyl)amino group, N-(2-fluorophenyl)amino group,N-(3-fluorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(2-chlorophenyl)amino group, N-(3-chlorophenyl)amino group,N-(4-chlorophenyl)amino group, N-(indan-2-yl)amino group,N-(1-phenylethyl)amino group, N-[1-(2-fluorophenyl)ethyl]amino group,N-[1-(3-fluorophenyl)ethyl]amino group, N-[1-(4-fluorophenyl)ethyl]aminogroup, N-[1-(2-chlorophenyl)ethyl]amino group,N-[1-(3-chlorophenyl)ethyl]amino group, N-[1-(4-chlorophenyl)ethyl]aminogroup, N-(2-methylphenylmethyl)amino group,N-methyl-N-(2-methylphenylmethyl)amino group,N-(3-methylphenylmethyl)amino group,N-methyl-N-(3-methylphenylmethyl)amino group,N-(4-methylphenylmethyl)amino group,N-methyl-N-(4-methylphenylmethyl)amino group,N-(2-fluorophenylmethyl)amino group,N-(2-fluorophenylmethyl)-N-methylamino group,N-(3-fluorophenylmethyl)amino group,N-(3-fluorophenylmethyl)-N-methylamino group,N-(4-fluorophenylmethyl)amino group,N-(4-fluorophenylmethyl)-N-methylamino group,N-(2-chlorophenylmethyl)amino group,N-(2-chlorophenylmethyl)-N-methylamino group,N-(3-chlorophenylmethyl)amino group,N-(3-chlorophenylmethyl)-N-methylamino group,N-(4-chlorophenylmethyl)amino group,N-(4-chlorophenylmethyl)-N-methylamino group,N-(2,3-difluorophenylmethyl)amino group,N-(2,3-difluorophenylmethyl)-N-methylamino group,N-(2,4-difluorophenylmethyl)amino group,N-(2,4-difluorophenylmethyl)-N-methylamino group,N-(2,5-difluorophenylmethyl)amino group,N-(2,5-difluorophenylmethyl)-N-methylamino group,N-(3,4-difluorophenylmethyl)amino group,N-(3,4-difluorophenylmethyl)-N-methylamino group,N-(3,5-difluorophenylmethyl)amino group,N-(3,5-difluorophenylmethyl)-N-methylamino group,N-(2,3-dichlorophenylmethyl)amino group,N-(2,3-dichlorophenylmethyl)-N-methylamino group,N-(2,4-dichlorophenylmethyl)amino group,N-(2,4-dichlorophenylmethyl)-N-methylamino group,N-(2,5-dichlorophenylmethyl)amino group,N-(2,5-dichlorophenylmethyl)-N-methylamino group,N-(2,6-dichlorophenylmethyl)amino group,N-(2,6-dichlorophenylmethyl)-N-methylamino group,N-(3,4-dichlorophenylmethyl)amino group,N-(3,4-dichlorophenylmethyl)-N-methylamino group,N-(3,5-dichlorophenylmethyl)amino group,N-(3,5-dichlorophenylmethyl)-N-methylamino group,N-[2-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[2-(trifluoromethyl)phenylmethyl]amino group,N-[3-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[3-(trifluoromethyl)phenylmethyl]amino group,N-[4-(trifluoromethyl)phenylmethyl]amino group,N-methyl-N-[4-(trifluoromethyl)phenylmethyl]amino group, 1-pyrrolidinogroup, 1-(4-methylpiperidino) group, 1-homopiperidino group, or4-morpholino group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ represents carbon atom substituted with Zx, and C²and C⁶ represent unsubstituted ring-constituting carbon atom.

Zx represents N-methylamino group, N-ethylamino group, N-propylaminogroup, N-isopropylamino group, N,N-dimethylamino group, N,N-diethylaminogroup, formylamino group, acetylamino group, carbamoylamino group,mesylamino group, and N,N-dimethylsulfamoylamino group.

Rs represents —O-Rx. Rx represents a group as any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ may be replaced with V, and C² and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, and Zxrepresents a group as any one of chlorine atom, bromine atom, methylgroup, hydroxyl group, methoxy group, amino group, N-methylamino group,N-ethylamino group, N-propylamino group, N-isopropylamino group,N,N-dimethylamino group, N,N-diethylamino group, formylamino group,acetylamino group, carbamoylamino group, mesylamino group, andN,N-dimethylsulfamoylamino group.

Rs represents —O-Rc. p in Rc represents an integer of 2, and A⁴represents a single bond or methylene. A⁵ represents —C(O)—, —C(S)—, or—S(O)₂—. Rd represents a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenylgroup, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, and 4-fluorophenylmethyl group. Rerepresents a group as any one of isopropyl group, butyl group, isobutylgroup, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexylgroup, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group,t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group,cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxygroup, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxygroup, 4-fluorophenyloxy group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,pyrrolidino group, piperidino group, and morpholino group.

AR represents a group as any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group.

The group Y represents hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ may be replaced with V, and C² and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, Zx isany one of fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group,

Rs represents -D-Rx and D represents a single bond. Rx is butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenylgroup, 2,3-dimethylphenyl group, 3,5-dimethylphenyl group,2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group,2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group,2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group,2,3-difluorophenyl group, 2,4-difluorophenyl group, 2,5-difluorophenylgroup, 3,4-difluorophenyl group, 2,3-dichlorophenyl group,2,4-dichlorophenyl group, 2,5-dichlorophenyl group, 2,6-dichlorophenylgroup, 3,4-dichlorophenyl group, 3,5-dichlorophenyl group,2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group,4-trifluoromethylphenyl group, 4-(N,N-dimethylamino)phenyl group,indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, furan-2-ylgroup, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group,pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group,naphthalen-1-yl group, naphthalen-2-yl group, 1H-indol-5-yl group,1-methyl-1H-indol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, biphenyl-2-yl group, biphenyl 3-ylgroup, biphenyl-4-yl group, 1-phenylethyl group, 1-(2-fluorophenyl)ethylgroup, 1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, C⁵ may be replaced with V, and C² and C⁶ representunsubstituted ring-constituting carbon atom.

V represents nitrogen atom, or carbon atom substituted with Zx, Zx isany one of fluorine atom, methyl group, hydroxyl group, amino group,N-methylamino group, or N,N-dimethylamino group,

Rs represents -D-Rx and D represents a single bond. Rx is phenyl group,2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group,2,3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenylgroup, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenylgroup, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, 2,3-difluorophenyl group,2,4-difluorophenyl group, 2,5-difluorophenyl group, 3,4-difluorophenylgroup, 2,3-dichlorophenyl group, 2,4-dichlorophenyl group,2,5-dichlorophenyl group, 2,6-dichlorophenyl group, 3,4-dichlorophenylgroup, 3,5-dichlorophenyl group, 2-trifluoromethylphenyl group,3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group,4-(N,N-dimethylamino)phenyl group, indan-2-yl group, 4-methylindan-2-ylgroup, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, furan-2-yl group, furan-3-yl group,thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group,pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group,naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-1H-indol-5-ylgroup, 1H-indazol-5-yl group, or 1-methyl-1H-indazol-5-yl group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

In another particularly preferred embodiment of the present invention,the compound represented by the formula (I) or a salt thereof satisfiesall of the following requirements.

Link represents —(CH₂)_(n)—, symbol n represents an integer of 2.

C³ represents carbon atom to which AR bonds, C⁴ represents carbon atomto which Rs bonds, and C², C⁵, and C⁶ represent unsubstitutedring-constituting carbon atom.

Rs represents -D-Rx and D represents a single bond. Rx is phenyl group,2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group,2,3-dimethylphenyl group, 3,5-dimethylphenyl group, 2-methoxyphenylgroup, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-fluorophenylgroup, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, 2,3-difluorophenyl group,2,4-difluorophenyl group, 2,5-difluorophenyl group, 3,4-difluorophenylgroup, 2,3-dichlorophenyl group, 2,4-dichlorophenyl group,2,5-dichlorophenyl group, 2,6-dichlorophenyl group, 3,4-dichlorophenylgroup, 3,5-dichlorophenyl group, 2-trifluoromethylphenyl group,3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group,4-(N,N-dimethylamino)phenyl group, indan-2-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, naphthalen-1-yl group,naphthalen-2-yl group, 1H-indol-5-yl group, 1-methyl-1H-indol-5-ylgroup, 1H-indazol-5-yl group, or 1-methyl-1H-indazol-5-yl group,

AR is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, and

Y is hydrogen atom, methyl group, or ethyl group.

Compound (I) of the present invention may have one or more asymmetriccarbons depending on types of substituents. For example, as for acompound wherein the group Rs contains one or more asymmetric carbons,two kinds of optical isomers exist when the number of asymmetric carbonis 1, and when the number of asymmetric carbons is 2, four kinds ofoptical isomers and two kinds of diastereomers exist. Pure stereoisomersincluding optical isomers and diastereoisomers, any mixtures thereof,racemates and the like of the stereoisomers fall within the scope of thepresent invention. Further, Compound (I) of the present invention mayexist as geometrical isomers based on a cycloalkyl ring structure, andany geometrical isomers in pure forms, and any mixtures of thegeometrical isomers also fall within the scope of the present invention.Mixtures such as racemates may sometimes be preferred from a viewpointof easiness for manufacture.

As a salt of Compound (I) of the present invention, a pharmaceuticallyacceptable salt is preferred. It is meant that, when at least one of theconditions (1) to (3) is satisfied: (1) Y is hydrogen atom; (2) thegroup AR contains carboxyl group or phenolic hydroxyl group; (3) thegroup Zx is phenolic hydroxyl group, and the like, then the compoundforms 1 to 3 alkali salts depending on the number of acidic groups.Examples the alkali salts include, for example, salts with inorganicbases such as sodium and ammonia and salts with organic bases such astriethylamine.

Alternatively, it is meant that, when at least one of the conditions (1)to (4) is satisfied: (1) the group Rs has properties as a base as in acompound wherein Rs contains a substituted or unsubstituted amino groupand the like; (2) AR itself is a cyclic substituent having properties asa base; (3) the group Ar contains a substituted or unsubstituted aminogroup; (4) any carbon atom in the aromatic ring (E) is replaced with V,and V is nitrogen atom, V is carbon atom substituted with Zx, and Zx isa substituted or unsubstituted amino group and the like, then thecompound forms 1 to 4 acidic salts depending on the number of basicgroups. Examples of the acidic salts include, for example, salts withinorganic acids such as hydrochloric acid and sulfuric acid and saltswith organic acids such as acetic acid and citric acid.

C²′, C³′, C⁴′, C⁵′, and C⁶′ in the aromatic ring (E′) in theaforementioned formula (II) each represent a ring-constituting carbonatom. Among them, any ring-constituting carbon atom to which Rs′ and Gdo not bind may be replaced with V′. The substitution positions of Rs′,G, and V′ are similar to those described in the explanations of thesubstitution positions of Rs (corresponding to the position of Rs′), AR(corresponding to the position of the group G), and V (corresponding tothe position of V′) in the aforementioned formula (I).

V′ represents nitrogen atom, or represents carbon atom substituted withZx′. Zx′ has the same meaning as that of Zx, provided that when Zxcontains hydroxyl group (OH), the hydroxyl group may be protected withRp¹, and when Zx contains amino group (NH), the amino group may beprotected with Rp².

Rs′ represents -D-Rx′ or —N(Ry′)(Rz′). -D-Rx′ and —N(Ry′)(Rz′) have thesame meanings as those of -D-Rx and —N(Ry)(Rz) mentioned above,respectively. Provided that when -D-Rx and —N(Ry)(Rz) contain hydroxylgroup, the hydroxyl group may be protected with Rp¹, and when -D-Rx and—N(Ry)(Rz) contains amino group (NH), the amino group may be protectedwith Rp².

Rp¹ represents, for example, a silyl group substituted with 3 ofidentical or different linear or branched saturated alkyl groups having1 to 4 carbon atoms or phenyl groups, tetrahydropyranyl group,tetrahydrofuryl group, allyl group, propargyl group, benzyl group whichmay be substituted with one T¹ or two or more identical or different T¹,—CH₂—U-Rp³, —C(O)Rp³, —C(O)ORp³, or the like. U represents oxygen atom,or sulfur atom, and Rp³ represents hydrogen atom, a linear or branchedsaturated alkyl group having 1 to 4 carbon atoms, trimethylsilylethylgroup, chloromethyl group, trichloromethyl group, trifluoromethyl group,9-fluorenylmethyl group, adamantyl group, allyl group, -A⁶-Qp, or thelike. Rp² represents, for example, benzyl group which may be substitutedwith one of T¹ or two or more of identical or different T¹, —C(O)Rp³,—C(O)ORp³, or the like. However, the protective groups of hydroxyl groupand amino group are not limited to these, and they can be chosen byreferring and examining methods for introduction of protective groupsand deprotection described in usual publications in the chemical field,for example, Protective Groups In Organic Synthesis, THIRD EDITION,published by John Wiley & Sons or the references cited therein.

G represents chlorine atom, bromine atom, iodine atom, mesylate group,triflate group, or an arenesulfonate group of which aromatic moiety maybe substituted with one of T¹ or two or more identical or different T¹.Examples of the arenesulfonate group include, for example,benzenesulfonate group, p-toluenesulfonate group, mesitylenesulfonategroup, 2,4,6-triisopropylbenzenesulfonate group,4-fluorobenzenesulfonate group, 2,5-dichlorobenzenesulfonate group,3-(trifluoromethyl)benzenesulfonate group, pentafluorobenzenesulfonategroup, 2-nitrobenzenesulfonate group, 2,4-dinitrobenzenesulfonate group,and the like. Preferred examples of G include chlorine atom, bromineatom, iodine atom, triflate group, and the like, and bromine atom andiodine atom are particularly preferred examples.

Y′ represents a lower alkyl group having 1 to 4 carbon atoms. Examplesof the lower alkyl group having 1 to 4 carbon atoms include methylgroup, ethyl group, propyl group, isopropyl group, butyl group, isobutylgroup, t-butyl group, and the like. Among these, methyl group, and ethylgroup are particularly preferred examples.

In the aforementioned formula (II), n and D have the same meaning asdefined above.

In a preferred embodiment, the compound represented by the formula (II)satisfies all of the following requirements.

Symbol n represents an integer of 1 to 3.

The group G binds to C²′, Rs′ binds to any of the atoms C³′, C⁴′ andC⁵′, and a ring-constituting carbon atom to which Rs′ does not bindamong C³′, C⁴′, and C⁵′ may be substituted with V′.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, chlorine atom, bromine atom,nitro group, methyl group, hydroxyl group, methoxy group, amino group,N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when the substituted Zx′ contains amino group, the amino group maybe protected with Rp².

Rs′ represents -D-Rx′ or —N(Ry′)(Rz′). D represents oxygen atom orsulfur atom. Rx′ represents butyl group, isobutyl group, 2-ethylbutylgroup, cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rbrepresents a group as any one of phenyl group, thienyl group, furylgroup, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthylgroup, indanyl group, indolyl group, and dihydrobenzodioxyl group. A²represents a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² represents oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ represents ethylene). R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q represents phenyl group, A¹ represents a single bond, orunsubstituted methylene, and A² represents a single bond, one of R² andR³ represents a substituent other than hydrogen atom). Symbol p in Rcrepresents an integer of 2 or 3, and A⁴ represents a single bond ormethylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, or a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Rerepresents any one of methyl group, ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, t-butyl group, cyclopropyl group,cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, andethyloxycarbonylamino group. Rz′ represents any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry′ represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz′ to form pyrrolidino group, piperidinogroup, piperazino group, morpholino group, pyrrol-1-yl group,imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogenatom to which they bonds. Provided that when -D-Rx′ or —N(Ry′)(Rz′)contains hydroxyl group (OH), the hydroxyl group may be protected withRp¹, and when -D-Rx′ or —N(Ry′)(Rz′) contains amino group, the aminogroup may be protected with Rp².

The group G represents chlorine atom, bromine atom, iodine atom, ortriflate group.

The group Y′ represents methyl group, or ethyl group.

In another preferred embodiment, the compound represented by the formula(II) satisfies all of the following requirements.

Symbol n represents an integer of 1 to 3.

The group G binds to C³′, Rs′ binds to any of the atoms C⁴′, C⁵′, andC⁶′, and a ring-constituting carbon atom to which Rs′ does not bindamong C⁴′, C⁵′ and C⁶′ may be replaced with V′.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, chlorine atom, bromine atom,nitro group, methyl group, hydroxyl group, methoxy group, amino group,N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when the substituted Zx′ contains amino group, the amino group maybe protected with Rp².

Rs′ represents -D-Rx′, or —N(Ry′)(Rz′). D represents oxygen atom orsulfur atom. Rx′ represents butyl group, isobutyl group, 2-ethylbutylgroup, cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rbrepresents a group as any one of phenyl group, thienyl group, furylgroup, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthylgroup, indanyl group, indolyl group, and dihydrobenzodioxyl group. A²represents a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² represents oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ represents ethylene). R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q represents phenyl group, A¹ represents a single bond, orunsubstituted methylene, and A² represents a single bond, one of R² andR³ represents a substituent other than hydrogen atom). Symbol p in Rcrepresents an integer of 2 or 3, and A⁴ represents a single bond ormethylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, or a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Rerepresents any one of methyl group, ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, t-butyl group, cyclopropyl group,cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, andethyloxycarbonylamino group. Rz′ represents any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry′ represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz′ to form pyrrolidino group, piperidinogroup, piperazino group, morpholino group, pyrrol-1-yl group,imidazol-1-yl group, or pyrazol-1-yl group together with nitrogen atom.Provided that when -D-Rx′ or —N(Ry′)(Rz′) contains hydroxyl group, thehydroxyl group may be protected with Rp¹, and -D-Rx′ or —N(Ry′)(Rz′)contains amino group, the amino group may be protected with Rp².

The group G represents chlorine atom, bromine atom, iodine atom, ortriflate group.

The group Y′ represents methyl group, or ethyl group.

In a particularly preferred embodiment, the compound represented by theformula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C²′ represents carbon atom to which the group G bonds, C³′ representscarbon atom to which Rs′ binds, C⁴′ may be replaced with V′, and C⁵′ andC⁶′ represent an unsubstituted ring-constituting carbon atom.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C²′ represents carbon atom to which the group G bonds, C⁴′ representscarbon atom to which Rs′ binds, C⁵′ may be replaced with V′, and C³′ andC⁶′ represent an unsubstituted ring-constituting carbon atom.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C³′ represents carbon atom to which the group G bonds, C⁵′ representscarbon atom to which Rs′ binds, and C²′, C⁴′ and C⁶′ represent anunsubstituted ring-constituting carbon atom.

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C³′ represents carbon atom to which the group G bonds, C⁴′ representscarbon atom to which Rs′ binds, C⁵′ represents nitrogen atom, and C²′and C⁶′ represent an unsubstituted ring-constituting carbon atom.

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C³′ represents carbon atom to which the group G bonds, C⁴′ representscarbon atom to which Rs′ binds, C⁶′ represents carbon atom substitutedwith Zx′, and

C²′ and C⁵′ represent an unsubstituted ring-constituting carbon atom.

Zx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C³′ represents carbon atom to which the group G bonds, C⁴′ representscarbon atom to which Rs′ binds, C⁶′ represents carbon atom substitutedwith Zx′, or unsubstituted carbon atom, and C²′ and C⁶′ represent anunsubstituted ring-constituting carbon atom.

Zx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —S-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C³′ represents carbon atom to which the group G bonds, C⁴′ representscarbon atom to which Rs′ binds, C⁵′ represents carbon atom substitutedwith Zx′, or unsubstituted ring-constituting carbon atom, and C²′ andC⁶′ represent an unsubstituted ring-constituting carbon atom.

Zx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —N(Ry′)(Rz′). Rz′ represents any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry′ represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz′ to form pyrrolidino group, piperidinogroup, or morpholino group together with the nitrogen atom to which theybonds. Provided that when —N(Ry′)(Rz′) contains hydroxyl group, thehydroxyl group may be protected with Rp¹, and when Ry′ or Rz′ containsamino group, the amino group may be protected with Rp².

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C³′ represents carbon atom to which the group G bonds, C⁴′ representscarbon atom to which Rs′ binds, C⁵′ represents carbon atom substitutedwith Zx′, and C²′ and C⁶′ represent an unsubstituted ring-constitutingcarbon atom.

Zx′ represents any one of N-methylamino group, N-ethylamino group,N-propylamino group, N-isopropylamino group, N,N-dimethylamino group,N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, and N,N-dimethylsulfamoylaminogroup. Provided that when the substituted Zx′ contains amino group (NH),the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

In another particularly preferred embodiment, the compound representedby the formula (II) satisfies all of the following requirements.

Symbol n represents an integer of 2.

C³′ represents carbon atom to which the group G bonds, C⁴′ representscarbon atom to which Rs′ binds, C⁵′ represents carbon atom substitutedwith Zx′, or unsubstituted carbon atom, and C²′ and C⁶′ represent anunsubstituted ring-constituting carbon atom.

Zx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ have the same meaning as that of Rc, providedthat when Rc contains hydroxyl group (OH), the hydroxyl group may beprotected with Rp¹. p in Rc represents an integer of 2, and A⁴represents a single bond or methylene. A⁵ represents —C(O)—, —C(S)—, or—S(O)₂—. Rd represents a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenylgroup, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, and 4-fluorophenylmethyl group. Rerepresents a group as any one of isopropyl group, butyl group, isobutylgroup, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexylgroup, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group,t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group,cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxygroup, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxygroup, 4-fluorophenyloxy group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,pyrrolidino group, piperidino group, and morpholino group.

The group G represents bromine atom, or iodine atom.

The group Y′ represents methyl group, or ethyl group.

C²′, C³′, C⁴′, C⁵′, and C⁶′ in the aromatic ring (E′) in theaforementioned formula (III) each represent a ring-constituting carbonatom. Any ring-constituting carbon atom to which Rs′ and AR′ do not bondamong them may be replaced with V′. The substitution positions of Rs′,AR′, and V′ are similar to those described in the explanations of thesubstitution positions of Rs (corresponding to the position of Rs′), AR(corresponding to the position of the group AR′), and V (correspondingto the position of V′) in the aforementioned formula (I).

AR′ has the same meaning as that of AR mentioned above, provided thatwhen AR contains hydroxyl group, the hydroxyl group may be protectedwith Rp¹. In this case, the hydroxyl group includes OH in carboxyl group(COOH). When the substituted AR contains amino group, the amino grouprepresents a substituent, which may be protected with Rp². Examples ofthe amino group, which may be protected include NH present in a ringconstituting AR, for example, as in indole ring, indazole ring, and thelike.

Rs′, V, n, and D in the aforementioned formula (III) have the samemeanings as those defined above. Rp¹, and Rp² also have the samemeanings as those defined above.

In a preferred embodiment, the compound represented by the formula (III)satisfies all of the following requirements.

AR′ binds to C²′, Rs′ binds to any of the atoms C³′, C⁴′, and C⁵′, and aring-constituting carbon atom to which Rs′ does not bind among C³′, C⁴′,and C⁶′ may be replaced with V′.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, chlorine atom, bromine atom,nitro group, methyl group, hydroxyl group, methoxy group, amino group,N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when the substituted Zx′ contains amino group, the amino group maybe protected with Rp².

Rs′ represents -D-Rx′ or —N(Ry′)(Rz′). D represents oxygen atom orsulfur atom. Rx′ represents butyl group, isobutyl group, 2-ethylbutylgroup, cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rbrepresents a group as any one of phenyl group, thienyl group, furylgroup, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthylgroup, indanyl group, indolyl group, and dihydrobenzodioxyl group. A²represents a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² represents oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ represents ethylene). R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q represents phenyl group, A¹ represents a single bond, orunsubstituted methylene, and A² represents a single bond, one of R² andR³ represents a substituent other than hydrogen atom). Symbol p in Rcrepresents an integer of 2 or 3, and A⁴ represents a single bond ormethylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, or a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Rerepresents any one of methyl group, ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, t-butyl group, cyclopropyl group,cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, andethyloxycarbonylamino group. Rz′ represents butyl group, isobutyl group,2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptylgroup, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenylgroup, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group,4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group,4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group,5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group,5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group,5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group,5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group,5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group,5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group,5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group,5,6-dimethoxyindan-2-yl group, 1-phenylethyl group,1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group,1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group,1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group,2-methylphenylmethyl group, 3-methylphenylmethyl group,4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group,3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group,3-fluorophenylmethyl group, 4-fluorophenylmethyl group,2-chlorophenylmethyl group, 3-chlorophenylmethyl group,4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group,2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group,3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group,2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group,2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group,3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group,2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethylgroup, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethylgroup, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group,2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group,2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group,2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group,2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group,2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry′ represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz to form pyrrolidino group, piperidinogroup, piperazino group, morpholino group, pyrrol-1-yl group,imidazol-1-yl group, or pyrazol-1-yl group together with the nitrogenatom to which they bond. However, -D-Rx′ or —N(Ry′)(Rz′) containshydroxyl group, the hydroxyl group may be protected with Rp¹, and when-D-Rx′ or —N(Ry′)(Rz′) contains amino group, the amino group may beprotected with Rp².

AR′ represents any one of naphthalen-2-yl group, naphthalen-1-yl group,benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, and 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of identical or different Xa). The substituent Xa representsa group as any one of oxo group, thioxo group, fluorine atom, chlorineatom, trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group. Provided that when AR′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whensubstituted AR′ contains amino group, the amino group may be protectedwith Rp².

In another preferred embodiment, the compound represented by the formula(III) satisfies all of the following requirements.

AR′ binds to C³′, Rs′ binds to any of the ring-constituting carbon atomsC⁴′, C⁵′, and C⁶′, and a ring-constituting carbon atom to which Rs′ doesnot bind among C⁴′, C⁵′, and C⁶′ may be replaced with V′.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, chlorine atom, bromine atom,nitro group, methyl group, hydroxyl group, methoxy group, amino group,N-methylamino group, N-ethylamino group, N-propylamino group,N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group,formylamino group, acetylamino group, carbamoylamino group, mesylaminogroup, and N,N-dimethylsulfamoylamino group, provided that when Zx′contains hydroxyl group, the hydroxyl group may be protected with Rp¹,and when the substituted Zx′ contains amino group, the amino group maybe protected with Rp².

Rs′ represents -D-Rx′ or —N(Ry′)(Rz′). D represents oxygen atom orsulfur atom. Rx′ represents butyl group, isobutyl group, 2-ethylbutylgroup, cyclopentyl group, cyclohexyl group, cycloheptyl group,cyclopentylmethyl group, cyclohexylmethyl group, 2-cyclopentylethylgroup, or 2-cyclohexylethyl group, or represents Rb or Rc. Q in Rbrepresents a group as any one of phenyl group, thienyl group, furylgroup, pyridyl group, oxazolyl group, naphthyl group, tetrahydronaphthylgroup, indanyl group, indolyl group, and dihydrobenzodioxyl group. A²represents a single bond, oxygen atom, sulfur atom, —N(methyl)-, or—N(ethyl)- (provided that when A² represents oxygen atom, sulfur atom,—N(methyl)-, or —N(ethyl)-, A¹ represents ethylene). R² and R³independently represent hydrogen atom, methyl group, fluorine atom,chlorine atom, trifluoromethyl group, methoxy group, dimethylaminogroup, acetylamino group, or methylsulfonylamino group (provided thatwhen Q represents phenyl group, A¹ represents a single bond, orunsubstituted methylene, and A² represents a single bond, one of R² andR³ represents a substituent other than hydrogen atom). Symbol p in Rcrepresents an integer of 2 or 3, and A⁴ represents a single bond ormethylene. A⁵ represents —C(O)—, —C(S)—, or —S(O)₂—. Rd representshydrogen atom, or a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopropylmethyl group, cyclopentyl group, cyclopentylmethylgroup, cyclohexyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group, benzylgroup, 4-chlorophenylmethyl group, 4-fluorophenylmethyl group,pyridin-2-yl group, pyridin-3-yl group, and pyridin-4-yl group. Rerepresents any one of methyl group, ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, t-butyl group, cyclopropyl group,cyclopentyl group, cyclohexyl group, cyclopentylmethyl group,cyclohexylmethyl group, phenyl group, 4-methylphenyl group,4-chlorophenyl group, 4-fluorophenyl group, phenylmethyl group,4-chlorophenylmethyl group, 4-fluorophenylmethyl group, pyridin-2-ylgroup, pyridin-3-yl group, pyridin-4-yl group, furan-2-yl group,furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, methoxygroup, ethoxy group, propyloxy group, isopropyloxy group, butyloxygroup, isobutyloxy group, t-butyloxy group, cyclopropyloxy group,cyclopentyloxy group, cyclohexyloxy group, cyclopentylmethyloxy group,cyclohexylmethyloxy group, phenyloxy group, 4-methylphenyloxy group,4-chlorophenyloxy group, 4-fluorophenyloxy group, thiomethoxy group,amino group, N-methylamino group, N,N-dimethylamino group, N-ethylaminogroup, N,N-diethylamino group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,N-(pyridin-2-yl)amino group, N-(pyridin-3-yl)amino group,N-(pyridin-4-yl)amino group, N-(furan-2-yl)amino group,N-(furan-3-yl)amino group, N-(thiophen-2-yl)amino group,N-(thiophen-3-yl)amino group, pyrrolidino group, piperidino group,morpholino group, methyloxycarbonylamino group, andethyloxycarbonylamino group. Rz′ represents any one of butyl group,isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, 2-(N-ethyl-N-phenylamino)ethylgroup, isobutyryl group, isopropylthiocarbonyl group, isopropylsulfonylgroup, valeryl group, butylthiocarbonyl group, isovaleryl group,isobutylthiocarbonyl group, pivaloyl group, t-butylthiocarbonyl group,cyclopropylcarbonyl group, cyclopropylthiocarbonyl group,cyclopentylcarbonyl group, cyclopentylthiocarbonyl group,cyclohexylcarbonyl group, cyclohexylthiocarbonyl group,cyclopentylmethylcarbonyl group, cyclopentylmethylthiocarbonyl group,cyclohexylmethylcarbonyl group, cyclohexylmethylthiocarbonyl group,benzoyl group, thiobenzoyl group, phenylsulfonyl group,4-methylphenylcarbonyl group, 4-methylphenylthiocarbonyl group,4-methylphenylsulfonyl group, 4-chlorophenylcarbonyl group,4-chlorophenylthiocarbonyl group, 4-fluorophenylcarbonyl group,4-fluorophenylthiocarbonyl group, isopropyloxycarbonyl group,N-isopropylcarbamoyl group, N-isopropylthiocarbamoyl group,butyloxycarbonyl group, N-butylcarbamoyl group, N-butylthiocarbamoylgroup, isobutyloxycarbonyl group, N-isobutylcarbamoyl group,N-isobutylthiocarbamoyl group, t-butyloxycarbonyl group,N-t-butylcarbamoyl group, N-t-butylthiocarbamoyl group,cyclopropyloxycarbonyl group, N-cyclopropylcarbamoyl group,N-cyclopropylthiocarbamoyl group, cyclopentyloxycarbonyl group,N-cyclopentylcarbamoyl group, N-cyclopentylthiocarbamoyl group,cyclohexyloxycarbonyl group, N-cyclohexylcarbamoyl group,N-cyclohexylthiocarbamoyl group, cyclopentylmethyloxycarbonyl group,cyclohexylmethyloxycarbonyl group, phenyloxycarbonyl group,N-phenylcarbamoyl group, N-phenylthiocarbamoyl group,4-methylphenyloxycarbonyl group, N-(4-methylphenyl)carbamoyl group,N-(4-methylphenyl)thiocarbamoyl group, 4-chlorophenyloxycarbonyl group,N-(4-chlorophenyl)carbamoyl group, N-(4-chlorophenyl)thiocarbamoylgroup, 4-fluorophenyloxycarbonyl group, N-(4-fluorophenyl)carbamoylgroup, N-(4-fluorophenyl)thiocarbamoyl group, (pyrrolidino-1-yl)carbonylgroup, (piperidino-1-yl)carbonyl group, and (morpholino-4-yl)carbonylgroup. Ry′ represents hydrogen atom, methyl group, ethyl group, orisobutyl group, or binds to Rz′ to form pyrrolidino group, piperidinogroup, piperazino group, morpholino group, pyrrol-1-yl group,imidazol-1-yl group, or pyrazol-1-yl group together with nitrogen atom.Provided that when -D-Rx′ or —N(Ry′)(Rz′) contains hydroxyl group, thehydroxyl group may be protected with Rp¹, and when -D-Rx′ or—N(Ry′)(Rz′) contains amino group, the amino group may be protected withRp².

AR′ represents any one of naphthalen-2-yl group, naphthalen-1-yl group,benzofuran-5-yl group, benzofuran-4-yl group, benzofuran-2-yl group,benzo[b]thiophen-5-yl group, benzo[b]thiophen-4-yl group,benzo[b]thiophen-2-yl group, indol-5-yl group, indol-4-yl group,indol-6-yl group, benzothiazol-6-yl group, benzothiazol-7-yl group,benzothiazol-5-yl group, benzothiazol-4-yl group,dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-yl group,dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-yl group,quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-1H-quinolin-6-yl group,dihydro-1H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoquinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5-yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5]thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3-b]pyridin-4-yl group,1,3-dihydrobenzimidazol-5-yl group, 1,3-dihydrobenzimidazol-4-yl group,dihydro-3H-benzoxazol-6-yl group, dihydro-3H-benzoxazol-7-yl group,dihydro-3H-benzoxazol-5-yl group, dihydro-3H-benzoxazol-4-yl group,phthalazin-6-yl group, phthalazin-5-yl group, [1,8]naphthalidin-3-ylgroup, [1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2-ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5-ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, and 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of identical or different Xa). The substituent Xa representsa group as any one of oxo group, thioxo group, fluorine atom, chlorineatom, trifluoromethyl group, methyl group, ethyl group, propyl group,2-hydroxyethyl group, carboxymethyl group, 2-carboxyethyl group,N,N-dimethylcarbamoylmethyl group, hydroxyl group, methoxy group,2-hydroxyethyloxy group, carboxymethyloxy group, 2-carboxyethyloxygroup, N,N-dimethylcarbamoylmethyloxy group, amino group, methylaminogroup, dimethylamino group, 2-hydroxyethylamino group, carbamoylaminogroup, acetylamino group, furan-2-carboxyamino group,2-hydroxyacetylamino group, 2-aminoacetylamino group,methylsulfonylamino group, (N,N-dimethylsulfamoyl)amino group,methanesulfonyl group, sulfamoyl group, N-methylsulfamoyl group,N,N-dimethylsulfamoyl group, carboxyl group, acetyl group, carbamoylgroup, and N,N-dimethylcarbamoyl group. Provided that when AR′ containshydroxyl group, the hydroxyl group may be protected with Rp¹, and whensubstituted AR′ contains amino group, the amino group may be protectedwith Rp².

In a particularly preferred embodiment, the compound represented by theformula (III) satisfies all of the following requirements.

C²′ represents carbon atom to which AR′ binds, C³′ represents carbonatom to which Rs′ binds, C⁴′ may be replaced with V′, and C⁵′ and C⁶′represent an unsubstituted ring-constituting carbon atom.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR′ represents any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group. Provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when substituted AR′contains amino group, the amino group may be protected with Rp².

In another particularly preferred embodiment, the compound representedby the formula (III) satisfies all of the following requirements.

C²′ represents carbon atom to which AR′ binds, C⁴′ represents carbonatom to which Rs′ binds, C⁵′ may be replaced with V′, and C³′ and C⁶′represent an unsubstituted ring-constituting carbon atom.

V′ represents nitrogen atom, or carbon atom substituted with Zx′, andZx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group. Providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR′ represents any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group. Provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when substituted AR′contains amino group, the amino group may be protected with Rp².

In another particularly preferred embodiment, the compound representedby the formula (III) satisfies all of the following requirements.

C³′ represents carbon atom to which AR′ binds, C⁵′ represents carbonatom to which Rs′ binds, and C²′, C⁴′ and C⁶′ represent an unsubstitutedring-constituting carbon atom.

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group

AR′ represents any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group. Provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when substituted AR′contains amino group, the amino group may be protected with Rp².

In another particularly preferred embodiment, the compound representedby the formula (III) satisfies all of the following requirements.

C³′ represents carbon atom to which AR′ binds, C⁴′ represents carbonatom to which Rs′ binds, C⁵′ represents nitrogen atom, and C²′ and C⁶′represent an unsubstituted ring-constituting carbon atom.

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR′ represents any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group. Provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when substituted AR′contains amino group, the amino group may be protected with Rp².

In another particularly preferred embodiment, the compound representedby the formula (III) satisfies all of the following requirements.

C³′ represents carbon atom to which AR′ binds, C⁴′ represents carbonatom to which Rs′ binds, C⁶′ represents carbon atom substituted withZx′, and C²′ and C⁵′ represent an unsubstituted ring-constituting carbonatom.

Zx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR′ represents any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group. Provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when substituted AR′contains amino group, the amino group may be protected with Rp².

In another particularly preferred embodiment, the compound representedby the formula (III) satisfies all of the following requirements.

C³′ represents carbon atom to which AR′ binds, C⁴′ represents carbonatom to which Rs′ binds, C⁵′ represents carbon atom substituted withZx′, and C²′ and C⁶′ represent an unsubstituted ring-constituting carbonatom.

Zx′ represents any one of N-methylamino group, N-ethylamino group,N-propylamino group, N-isopropylamino group, N,N-dimethylamino group,N,N-diethylamino group, formylamino group, acetylamino group,carbamoylamino group, mesylamino group, and N,N-dimethylsulfamoylaminogroup. Provided that when the substituted Zx′ contains amino group (NH),the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ represents any one of butyl group, isobutylgroup, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group,cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group,2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group,3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group,3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group,4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group,1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, and2-(N-ethyl-N-phenylamino)ethyl group.

AR′ represents any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group. Provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when substituted AR′contains amino group, the amino group may be protected with Rp².

In another particularly preferred embodiment, the compound representedby the formula (III) satisfies all of the following requirements.

C³′ represents carbon atom to which AR′ binds, C⁴′ represents carbonatom to which Rs′ binds, C⁵′ represents carbon atom substituted withZx′, or an unsubstituted ring-constituting carbon atom, and C²′ and C⁶′represent an unsubstituted ring-constituting carbon atom.

Zx′ represents any one of fluorine atom, methyl group, hydroxyl group,amino group, N-methylamino group, and N,N-dimethylamino group, providedthat when Zx′ contains hydroxyl group, the hydroxyl group may beprotected with Rp¹, and when the substituted Zx′ contains amino group,the amino group may be protected with Rp².

Rs′ represents —O-Rx′. Rx′ have the same meaning as that of Rc, providedthat when Rc contains hydroxyl group, the hydroxyl group may beprotected with Rp¹. p in Rc represents an integer of 2, and A⁴represents a single bond or methylene. A⁵ represents —C(O)—, —C(S)—, or—S(O)₂—. Rd represents a group as any one of methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, cyclopropylgroup, cyclopentyl group, cyclohexyl group, phenyl group, 4-methylphenylgroup, 4-chlorophenyl group, 4-fluorophenyl group, benzyl group,4-chlorophenylmethyl group, and 4-fluorophenylmethyl group. Rerepresents a group as any one of isopropyl group, butyl group, isobutylgroup, t-butyl group, cyclopropyl group, cyclopentyl group, cyclohexylgroup, cyclopentylmethyl group, cyclohexylmethyl group, phenyl group,4-methylphenyl group, 4-chlorophenyl group, 4-fluorophenyl group,propyloxy group, isopropyloxy group, butyloxy group, isobutyloxy group,t-butyloxy group, cyclopropyloxy group, cyclopentyloxy group,cyclohexyloxy group, cyclopentylmethyloxy group, cyclohexylmethyloxygroup, phenyloxy group, 4-methylphenyloxy group, 4-chlorophenyloxygroup, 4-fluorophenyloxy group, N-propylamino group, N-isopropylaminogroup, N-butylamino group, N-isobutylamino group, N-t-butylamino group,N-cyclopropylamino group, N-cyclopentylamino group, N-cyclohexylaminogroup, N-phenylamino group, N-(4-methylphenyl)amino group,N-(4-chlorophenyl)amino group, N-(4-fluorophenyl)amino group,pyrrolidino group, piperidino group, and morpholino group.

AR′ represents any one of naphthalen-2-yl group,6-hydroxynaphthalen-2-yl group, 6-methoxynaphthalen-2-yl group,6-(2-hydroxyethyloxy)naphthalen-2-yl group, 6-aminonaphthalen-2-ylgroup, 6-(N-methylamino)naphthalen-2-yl group,6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, 3-hydroxy-1H-indazol-5-yl group,3-hydroxy-1-methyl-1H-indazol-5-yl group,1-ethyl-3-hydroxy-1H-indazol-5-yl group, imidazo[1,2-a]pyridin-6-ylgroup, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, andbenzoxazol-5-yl group. Provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when substituted AR′contains amino group, the amino group may be protected with Rp².

Compound (I) of the present invention can be produced by, for example,employing the reactions according to the following various methods.

[Preparation Method 1] (Step a-1)

As shown in the following scheme 1:

a compound of the present invention represented by the formula (Ia′)wherein Y represents a lower alkyl group having 1 to 4 carbon atoms, andRs, AR, and V on or in the aromatic ring (E) may be protected[hereinafter simply referred to as “Compound (Ia′)”], which falls withinthe scope of Compound (I) of the present invention, can be prepared byreacting a compound represented by the formula (II) [simply referred toas “Compound (II)” hereinafter] with a boronic acid derivativerepresented by the formula (IV) [hereinafter simply referred to as“Compound (IV)”]. n, C²′ to C⁶, Rs′, AR′, Y′ and G in the formulas havethe same meanings as defined above. In the formula of Compound (IV), L¹and L² independently represent hydroxyl group, an alkoxyl group having 1to 8 carbon atoms (e.g., methoxy group, ethoxy group, propoxy group,isopropoxy group, cyclohexyloxy group), or a substituted orunsubstituted phenyloxy group, or L¹ and L² bind to each other torepresent a 5- or 6-membered cyclic ester of an arylboric acid (e.g.,9-borabicyclo[3,3,1]nonane, 1,3,2-dioxaborolane,4,4,5,5-tetramethyl-1,3,2-dioxaborolane), which forms a ring containingboron atom [this ring may be saturated or unsaturated, may be a ringcontaining a heteroatom other than boron (e.g., oxygen atom), and may befurther substituted].

Further, as shown in the following scheme 2:

an example of the method for preparing Compound (Ia′) includes a methodof reacting a combination of a compound represented by the formula (V)[hereinafter simply referred to as “Compound (V)”] and a compoundrepresented by the formula (VI) [hereinafter simply referred to as“Compound (VI)”].

Examples include a method of preparing Compound (Ia′) by performing theSuzuki reaction described in, for example, Jikken Kagaku Koza, 4thEdition (edited by Chemical Society of Japan, published by Maruzen Co.,Ltd.), vol. 25, p. 403 with a combination mentioned either in the scheme1 or scheme 2 or the both. A specific example includes a reaction ofCompound (II) [or Compound (V)] with Compound (IV) [or Compound (VI)] ina solvent in the presence of a commercially available palladium catalystor a catalyst prepared from a palladium complex and a ligand, and abase.

As the palladium catalyst, a commercially available catalyst such astetrakis(triphenylphosphine)palladium,tetrakis(methyldiphenylphosphine)palladium,dichlorobis(triphenylphosphine)palladium,dichlorobis(tri-o-tolylphosphine)palladium,dichlorobis(tricyclohexylphosphine)palladium,dichlorobis(triethylphosphine)palladium, palladium acetate, palladiumchloride, bis(acetonitrile)palladium chloride,tris(dibenzylideneacetone)dipalladium andbis(diphenylphosphinoferrocene)palladium chloride may be purchased andadded to the reaction system, per se, or a catalyst may be added whichis separately prepared from palladium acetate,tris(dibenzylideneacetone)dipalladium or the like and arbitrary ligandsand isolated. Further, a catalyst considered to actually participate inthe reaction may also be prepared by mixing palladium acetate,tris(dibenzylideneacetone)dipalladium or the like and arbitrary ligandsin the reaction system. The valence of palladium may be 0 or may be +2.Examples of the ligand include phosphine ligands such astrifurylphosphine, tri(o-tolyl)phosphine, tri(cyclohexyl)phosphine,tri(t-butyl)phosphine, dicyclohexylphenylphosphine,1,1′-bis(di-t-butylphosphino)ferrocene,2-dicyclohexylphosphino-2′-dimethylamino-1,1′-biphenyl and2-(di-t-butylphosphino)biphenyl and phosphine mimic ligands such asimidazol-2-ylidenecarbenes. Chemical equivalents of the palladiumcatalyst may be one equivalent or a catalytic amount, and the amount maypreferably be 0.01 to 20.0 mol %, and most preferably be 0.10 to 10.0mol %.

Examples of the base include sodium carbonate, potassium carbonate,cesium carbonate, cesium fluoride, potassium fluoride, potassiumphosphate, potassium acetate, triethylamine, potassium hydroxide, sodiumhydroxide, sodium methoxide, lithium methoxide and the like. Thereaction temperature is, for example, preferably 20° C. to 150° C., andparticularly preferable examples include 20° C. to 120° C.

The reaction system may be either a two-phase system of water and anorganic solvent, or a homogeneous system of a water-containing organicsolvent or an organic solvent. As for the organic solvent, examplesinclude uses of hydrocarbon-type solvents such as toluene, xylene andhexane, halogen-type solvents such as methylene chloride, sulfoxide-typesolvents such as dimethyl sulfoxide, amide-type solvents such asdimethylformamide, ether-type solvents such as tetrahydrofuran, dioxaneand diglyme, alcohol-type solvents such as methanol and ethanol,nitrile-type solvents such as acetonitrile, ketone-type solvents such asacetone and cyclohexanone, ester-type solvents such as ethyl acetate,heterocyclic-type solvents such as pyridine and the like. Two or morekinds of organic solvents may be mixed and used.

For the reaction conditions, Miyaura, N., Suzuki, A., Chemical Review,1995, vol. 95, p. 2457; Snieckus, V., Chemical Review, 1990, vol. 90, p.879 and the like and references cited therein can be referred to.

When hydroxyl group or amino group reactive under the aforementionedreaction conditions or inhibiting the reactions exists in the group AR′,Rs′ or V′ in the aromatic ring (E′), this substituent is preferablyprotected.

When a protective group of hydroxyl group or amino group exist in thegroup AR′, Rs′ or V′ in the aromatic ring (E′) of the compound (Ia′)prepared as described above, such a protective group can be eliminatedduring or after the preparation of Compound (Ia′) to convert thecompound into Compound (I) of the present invention. As for selection,introduction and deprotection of these protective groups of hydroxylgroup and amino group, ordinary chemical publications, for example,Protective Groups In Organic Synthesis THIRD EDITION, John Wiley & Sons)and references cited therein can be referred to.

[Preparation Method 1] (Step a-2)

As Compound (IV), a compound commercially available as a reagent may beused, or as shown in the following scheme 3:

the compound can be produced from Compound (VI), which is commerciallyavailable or can be synthesized by a known method or a similar methodthereto, according to the method described in the aforementionedreference (Chemical Review, vol. 95, p. 2457, 1995) or the methoddescribed in Satoh, Y. et al., SYNTHESIS, p. 1146, 1994 or according tothe references cited therein.

For example, examples include a method of preparing Compound (VI) byconverting Compound (VI) into a lithio-compound using an alkyl lithiumsuch as n-butyl lithium and t-butyl lithium, then reacting the productwith a trialkyl borate and treating the product with a mineral acid suchas hydrochloric acid, sulfuric acid, and phosphoric acid; and a methodof to preparing Compound (VI) by performing a cross-coupling reaction ofCompound (VI) and an (alkoxyl)diboron in the presence of a palladiumcatalyst and a base.

An example of the preparation method of Compound (V) includes a methodof subjecting Compound (II) to a reaction similar to that of theaforementioned Step a-2, as shown in the following scheme 4:

[Preparation Method 1] (Step b)

As shown in the following scheme 5:

a compound represented by the formula (IIh) (hereinafter simply referredto as “Compound (IIh)”), which correspond to the compounds (II) whereinG represents a halogen atom such as chlorine atom, bromine atom oriodine atom, can be prepared by halogenating a compound represented bythe formula (VII) [this compound is simply referred to as “Compound(VII)”], which is commercially available or can be prepared by a knownmethod or a method similar thereto. In the formula of Compound (IIh),the group Hal represents a halogen atom, which may be any of chlorineatom, bromine atom and iodine atom. As for the halogenation, examples ofchlorination include a preparation method described in ordinarypublications in the filed of chemistry, for example, Shin Jikken KagakuKoza (edited by Chemical Society of Japan, published by Maruzen Co.,Ltd.), vol. 14, p. 354. Examples of the method include a methodutilizing chlorine (Cl₂), a method utilizing sulfuryl chloride, and thelike. Examples of bromination include a preparation method described inordinary publications in the filed of chemistry, for example, ShinJikken Kagaku Koza (edited by Chemical Society of Japan, published byMaruzen Co., Ltd.), vol. 14, p. 354. Examples of the method include amethod utilizing bromine (Br₂), a method utilizing N-bromosuccinimide,and the like. Examples of iodination include a preparation methoddescribed in ordinary publications in the filed of chemistry, forexample, Shin Jikken Kagaku Koza (edited by Chemical Society of Japan,published by Maruzen Co., Ltd.), vol. 14, p. 423. Examples of the methodinclude a method utilizing iodine (I₂), a method utilizing potassiumtriiodide, and the like.

[Preparation Method 1] (Step c)

As shown in the following scheme 6:

a compound represented by the formula (IIs) (this compound ishereinafter simply referred to as “Compound (IIs)”), which correspondsto Compound (II) wherein G represents mesylate group, triflate group, oran arenesulfonate group, can be prepared by converting a compoundrepresented by the formula (VIII) (this compound is simply referred toas “Compound (VIII)”), which is commercially available or can beprepared by a known method or a method similar thereto, into a sulfonicacid ester. In the formula of Compound (IIs), the group Su representsmethanesulfonyl group, trifluoromethanesulfonyl group, or arenesulfonylgroup of which aromatic ring may be substituted with one of T¹ or two ormore of identical or different T¹. Examples of the method for theconversion into sulfonic acid ester include a preparation methoddescribed in ordinary publications in the filed of chemistry, forexample, Shin Jikken Kagaku Koza (edited by Chemical Society of Japan,published by Maruzen Co., Ltd.), vol. 14, p. 1793. Examples of themethod include a method utilizing sulfonyl chloride, a method utilizingsulfonic anhydride, and the like.

[Preparation Method 2] (Step d)

As shown in the following scheme 7:

a compound represented by the formula (Ib′) wherein Y representshydrogen atom, and Rs, AR, and V on or in the aromatic ring (E) may beprotected (this compound is hereinafter simply referred to as “Compound(Ib′)”), which constitutes a part of the scope of Compound (I) of thepresent invention, can be prepared by hydrolyzing Compound (Ia′) so asto convert the group OY′ into hydroxyl group.

For the reaction of converting Compound (Ia′) into Compound (Ib′), ingeneral, the compound is preferably reacted in a base. Further, for thereaction of converting Compound (Ia′) to Compound (Ib′), in general, thecompound is preferably reacted in an inert medium that does not inhibitthe reaction, preferably a polar solvent.

Examples of the base used in the above reaction include, for example,alkali metal bases such as sodium hydroxide, potassium hydroxide, sodiumcarbonate, potassium carbonate, sodium methoxide and potassiumt-butoxide and organic bases such as triethylamine. As for amounts ofthe bases, generally 1 to 20 moles, preferably 1 to 10 moles, for alkalimetal bases, or 1 to a large excess moles for organic bases based onCompound (Ia′).

Examples of the polar solvent include water, methanol, ethanol,tetrahydrofuran, dioxane and the like, and these solvents may be used asa mixture as required. As the reaction temperature, an appropriatetemperature of, for example, from room temperature to a refluxingtemperature of solvent is chosen. The reaction time is, for example,generally 0.5 to 72 hours, preferably 1 to 48 hours, when an alkalimetal base is used, or generally 5 hours to 14 days when an organic baseis used. Since progress of the reaction can be monitored by thin layerchromatography (TLC), high performance liquid chromatography (HPLC) orthe like, the reaction can generally be terminated appropriately so asto maximize the yield of Compound (Ib′).

For collection of Compound (Ib′) obtained as described above from thereaction solution as a free carboxylic acid, operations may preferablybe carried out by, when the polar solvent is a water-soluble solvent,evaporating the solvent, neutralizing the residue with an inorganic acidsuch as aqueous hydrochloric acid, dissolving the residue in awater-insoluble solvent, then washing the solution with a weakly acidicaqueous solution, water or the like, and evaporating the solvent. Whenthe polar solvent is a water-insoluble solvent, operations maypreferably carried out by neutralizing the reaction solution with aninorganic acid, washing the solution with a weakly acidic aqueoussolution, water or the like, and then evaporating the solvent.

Further, when Compound (Ib′) forms a salt with the base used after thereaction to give a solid, the salt of Compound (Ib′) can be obtained byisolation and purification of the solid in a conventional manner.

When a protective group of hydroxyl group or amino group exists in thegroup AR′, Rs′ or V′ in the aromatic ring (E′) of Compound (Ia′)prepared as described above, Compound (Ia′) can be converted intoCompound (I) of the present invention by removing the protective groupduring or after the preparation of Compound (Ia′).

[Preparation Method 3] (Step e)

As shown by the following scheme 8:

a compound represented by the formula (Ic′) [hereinafter simply referredto as “Compound (Ic′)”] as Compound (I) of the present invention whereinthe group Y represents Y″, and Rs, AR, and V in the aromatic ring (E)may be protected, can be produced by esterifying the carboxyl group(COOH) of Compound (Ib′) in a conventional manner. In the formula ofCompound (Ib′), Y″ represents a lower alkyl group having 1 to 4 carbonatoms, a —(CH₂)_(m)NR¹⁸R¹⁹ group, or —C(R²⁰)₂OC(O)A³R²¹.

Examples of the method for producing Compound (Ic′) include a method ofallowing Compound (Ib′) to react with an inorganic halide withoutsolvent or in an inert solvent to convert the compound into an acidhalide and then allowing the acid halide per se or the same dissolved inan inert solvent to react with an excess amount of hydroxide of thetargeted Y″. Examples of the inorganic halide used in this methodinclude thionyl chloride, phosphoryl chloride, phosphorus pentachloride,phosphorus trichloride and the like, and thionyl chloride is a preferredexample. Examples of an amount used include generally an equimolar to alarge excess amount, preferably 1.5 to 5 moles based on Compound (Ib′).Examples of the inert solvent used in this reaction include, forexample, halogenated hydrocarbons such as dichloromethane, chloroformand 1,2-dichloroethane, ethers such as tetrahydrofuran and dioxane, andbenzene compounds such as benzene, toluene, xylene and chlorobenzene.These solvents can be used, for example, each alone or as a mixedsolvent. In order to promote the reaction, a catalytic amount ofN,N-dimethylformamide may be added. As a reaction temperature, anappropriate temperature of from room temperature to a refluxingtemperature of the solvent is generally chosen. Examples of the reactiontime include generally 0.5 to 24 hours, preferably 1 to 6 hours.

Examples of the inert solvent used for the reaction with hydroxide ofthe targeted Y″ include, for example, halogenated hydrocarbons such asdichloromethane, chloroform and 1,2-dichloroethane, ethers such astetrahydrofuran and dioxane, and benzene compounds such as benzene,toluene, and xylene. The reaction can also be performed with an excessamount of the hydroxide of the targeted Y″ without using a solvent. Asthe reaction temperature, an appropriate temperature of from −10° C. toroom temperature is chosen. Examples of the reaction time includegenerally 0.5 to 24 hours, preferably 0.5 to 6 hours.

Other methods for producing Compound (Ic′) include, for example, the“esterification using an alcohol” described in Shin Jikken Kagaku Koza(edited by the Chemical Society of Japan, published by Maruzen Co.,Ltd.), vol. 14, p. 1002, “esterification using an O-alkylating agent”,ibid, the same volume, p. 1002, “esterification using an alkyl halide”,ibid, the same volume, p. 1008, “esterification reaction using adehydrating agent”, ibid, vol. 22, p. 45 and the like.

When hydroxyl group or amino group reactive under the aforementionedreaction conditions or inhibiting the reactions exists in AR′, Rs′ or V′in the aromatic ring (E′), this substituent is preferably protected.

When a protective group of hydroxyl group or amino group exist in AR′,Rs′ or V′ in the aromatic ring (E′) of the compound (Ic′) prepared asdescribed above, such a protecting group can be eliminated during orafter the preparation of Compound (Ic′) to convert the compound intoCompound (I) of the present invention.

[Preparation Method 4]

As shown in the following scheme 9:

a compound represented by the formula (Id′) (hereinafter this compoundis simply referred to as “Compound (Id′)”) as Compound (I) of thepresent invention wherein n in the methylene moiety is an integer of 2,and wherein Rs, AR, and V in the aromatic ring (E) may be protected, canalso be prepared by the method shown below.

[Preparation Method 4] (Step f)

Compound (Id′) can be prepared by reducing the double bond of a compoundrepresented by the formula (IX) (hereinafter this compound is simplyreferred to as “Compound (IX)”) using a reduction reaction described inordinary publications in the filed of chemistry. Examples of thereaction include a method of converting the double bond of Compound (IX)into a single bond by hydrogenation using a hydrogen source such ashydrogen gas, ammonium formate, and hydrazine hydrate in a singlesolvent or a mixed solvent of alcoholic-type solvents such as methanol,ester-type solvents such as ethyl acetate in the presence of a catalystsuch as palladium/carbon powder, platinum oxide (PtO₂), and activatednickel.

When hydroxyl group or amino group reactive under the aforementionedreaction conditions or inhibiting the reactions exists in AR′, Rs′ or V′in the aromatic ring (E′), this substituent is preferably protected.

When a protective group of hydroxyl group or amino group exist in AR′,Rs′ or V′ in the aromatic ring (E′) of the compound (Id′) prepared asdescribed above, such a protecting group can be eliminated during orafter the preparation of Compound (Id′) to convert the compound intoCompound (I) of the present invention.

[Preparation Method 4] (Step g)

Compound (IX) can be prepared from a compound represented by the formula(III) [hereinafter this compound is simply referred to as “Compound(III)”]. Examples of the preparation method include a method utilizingthe Horner-Emonds reaction described in Shin Jikken Kagaku Koza (editedby Chemical Society of Japan, published by Maruzen Co., Ltd.), vol. 14,p. 238. Specifically, the compound can be obtained by reacting Compound(III) with a commercially available dialkylphosphonoacetic acid ester inan inert solvent, for example, an alcohol-type solvent such as methanoland ethanol or ether-type solvent such as tetrahydrofuran anddimethoxyethane in the presence of a base such as sodium hydride andsodium alkoxide. As the reaction temperature, an appropriate temperatureof from −10° C. to a refluxing temperature of a solvent is generallychosen, and preferred examples include a temperature of from 0° C. toroom temperature. The reaction time is generally 1 to 16 hours,preferably 2 to 8 hours. Since progress of the reaction can be monitoredby thin layer chromatography (TLC), high performance liquidchromatography (HPLC) or the like, the reaction can generally beterminated appropriately so as to maximize the yield of Compound (IX).

[Preparation Method 4] (Step a)

As shown in the following scheme 10:

Compound (III) can be prepared by introducing the substituent AR′ into acompound represented by the formula (X) [hereinafter this compound issimply referred to as “Compound (X)”] according to any of the methodsdescribed in the step a-1 of the preparation method 1 mentioned above.

[Preparation Method 5]

As shown in the following scheme 11:

a compound represented by the formula (Ie′) [hereinafter this compoundis simply referred to as “Compound (Ie′)”], as Compound (I) of thepresent invention wherein n in the methylene moiety is an integer of 1,Y represents hydrogen atom, and Rs, AR, and V in the aromatic ring (E)may be protected, can also be prepared by the method shown below.

[Preparation Method 7] (Step d)

Specifically, Compound (Ie′) can be prepared by hydrolyzing nitrilegroup of a compound represented by the formula (XI) [hereinafter thiscompound is simply referred to as “Compound (XI)”] into carboxyl groupaccording to a method similar to the method shown in the step d of thepreparation method 2 mentioned above.

When a protective group of hydroxyl group or amino group exist in AR′,Rs′ or V′ in the aromatic ring (E′) of the compound (Ie′) prepared asdescribed above, such a protecting group can be eliminated during orafter the preparation of Compound (Ie′) to convert the compound intoCompound (I) of the present invention.

[Preparation Method 5] (Step h)

Compound (XI) can be produced from Compound (III) mentioned above. Forexample, Compound (III) is reacted with a trimethylsilyl cyanide using aLewis acid, particularly zinc iodide, as a catalyst in an inert solventsuch as tetrahydrofuran as described in Jikken Kagaku Koza, 4th Edition(edited by Chemical Society of Japan, published by Maruzen Co., Ltd.),vol. 20, p. 445. Then, the reduction reaction using a hydrosilanedescribed in Jikken Kagaku Koza, 4th Edition (edited by Chemical Societyof Japan, published by Maruzen Co., Ltd.), vol. 26, p. 197 is performed.Examples of the method of the reduction reaction include a method ofperforming the reduction with a hydrosilane such as triethylsilane and aprotonic acid such as trifluoroacetic acid or a Lewis acid such as borontrifluoride in a halogenated solvent such as dichloromethane.

The preparation method of Compound (I) is not limited to the methodsdescribed herein. For example, the compounds of the present inventioncan be produced by modifying or converting a substituent of a compoundserving as a precursor of the compounds according to a method or acombination of methods described in ordinary publications in the filedof chemistry.

Examples of the preparation method for Compound (I) of the presentinvention which contains an asymmetric carbon in the substituent Rsinclude a method of using a starting material in which a moietycorresponding to the asymmetric carbon in the substituent Rs is alreadyoptically active, which is commercially available (or can be prepared bya known method or a method similar thereto). A method is also availablein which the compound of the present invention or a precursor thereof isseparated as an optically active isomer in a conventional manner.Examples of such method include, for example, a method utilizing highperformance liquid chromatography (HPLC) using a chiral column, a methodcomprising condensation with an optically active regent to form adiastereomer, successive separation and purification, followed bydecomposition. When a precursor is separated to obtain an opticalisomer, optically active Compound (I) of the present invention can thenbe prepared by performing the aforementioned preparation methods.

When Compound (I) of the present invention contains an acidic functionalgroup such as carboxyl group or phenolic hydroxyl group, the compoundcan be converted into pharmaceutically acceptable salt (e.g., inorganicsalts with sodium, ammonia and the like, or organic salts withtriethylamine and the like) by a known means. For example, when aninorganic salt is to be obtained, it is preferable to dissolve Compound(I) of the present invention in water containing at least 1 equivalenceof hydroxide, carbonate, bicarbonate or the like corresponding to adesired inorganic salt. For the reaction, an inactive water-miscibleorganic solvent such as methanol, ethanol, acetone, and dioxane may bemixed. For example, by using sodium hydroxide, sodium carbonate, orsodium hydrogencarbonate, a solution of sodium salt can be obtained.

When Compound (I) of the present invention contains a basic functionalgroup such as amino group, or when Compound (I) of the present inventioncontains an aromatic ring which itself has properties of base (e.g.,pyridine ring), the compound can be converted into a pharmaceuticallyacceptable salt (e.g., salt with inorganic acids such as hydrochloricacid and sulfuric acid, or salts with organic acids such as acetic acidand citric acid) by a known means. For example, when an inorganic saltis to be obtained, it is preferable to dissolve Compound (I) of thepresent invention in water containing at least 1 equivalence of adesired inorganic acid. For the reaction, an inactive water-miscibleorganic solvent such as methanol, ethanol, acetone, and dioxane may bemixed. For example, by using hydrochloric acid, a solution ofhydrochloride can be obtained.

When a solid salt is desired, a solution may be evaporated, or awater-miscible organic solvent having polarity to some extent, such asbutanol or ethyl methyl ketone, can be added to obtain a solid saltthereof.

The various compounds disclosed by the present invention can be purifiedby known methods such as recrystallization, and variety ofchromatography techniques (column chromatography, flash columnchromatography, thin layer chromatography, high performance liquidchromatography).

Compound (I) of the present invention and pharmaceutically acceptablesalts thereof have an action of suppressing the production of both ofprostaglandins and leukotrienes. The action of suppressing theproduction of prostaglandins and/or leukotrienes includes, for example,an action of suppressing PGE₂ production, observed when cultured cellsof MG-63 which is a human osteosarcoma cell line are stimulated withIL-1β and/or PGD₂ and LTB₄ production observed when cultured cells ofRBL-2H3 which is a rat mastocytoma cell line are stimulated with IgE, by10% or more, preferably 30% or more, most preferably 50% or more,compared with a positive control at a concentration of the compound nothaving cytotoxicity. As for a mode of action at a molecular level, it isconsidered that the compound of the present invention inhibits both ofCOX-1 and/or COX-2, which produce prostaglandins, and 5-LO, whichproduces leukotrienes. It is also considered that the compound of thepresent invention suppresses the production of arachidonic acid byinhibiting enzymatic activity of type 2A, 4, or 5 PLA₂ involved inprostaglandin and leukotrien production.

It is considered that, in these molecular action mechanisms, Compound(I) of the present invention inhibits the enzymatic activity of type 4PLA₂. For the judgment, for example, the enzyme inhibitory actionagainst type 4 PLA₂ can be examined, and known methods for measuring theenzymatic activity of type 4 PLA₂ are preferably utilized [Clark et al.,Proceeding of National Academy of Science USA (Proc. Natl. Acad. Sci.USA), 1990, vol. 87, p. 7708; Gronich et al., Biochemical Journal(Biochem. J.), 1990, vol. 271, p. 37; Clark et al., Cell, 1991, vol. 65,p. 1043; Kramer et al., Journal of Biological Chemistry (J. Biol.Chem.), 1991, vol. 266, p. 5268]. The type 4 PLA₂ inhibitory action ofthe compounds of the present invention can be elucidated by employingthese methods.

Compounds (I) of the present invention and pharmaceutically acceptablesalts thereof inhibited mouse inflammatory edema, allergic edema, aceticacid writhing reaction, and rat adjuvant arthritis by oraladministration at a dose of 0.1 to 500 mg/kg, and caused no death of themice by oral administration at a dose of 500 mg/kg/day for 3 days.Therefore, they are safe compounds as drugs for mammals, preferablyhumans, pets or companion animals such as dogs and cats, and farmanimals, and they are useful substances as active ingredients ofmedicaments. Preferred examples of the medicaments for mammals,preferably humans, pets or companion animals such as dogs and cats, andfarm animals include agents for prophylactic and/or therapeutictreatment of various conditions, various diseases, and pathologicalconditions in which an acute or chronic inflammatory reaction resultedfrom production of prostaglandin and/or leukotriene is observed,specifically inflammatory diseases, allergic diseases, autoimmunediseases, and pain.

More specifically, the conditions or diseases include arthritis, chronicrheumatoid arthritis, malignant rheumatoid arthritis, juvenilerheumatoid arthritis, Felty's syndrome, adult Still's disease,osteoarthritis, synovitis, gout, slack of artificial joint implant,fervescence, common cold, algesia, burn, thermal injury, keloplasty,menstrual pain, dysmenorrhea, menstrual cramp, allergic reaction,allergic contact hypersensitivity, allergic rhinitis, pollinosis,allergic conjunctivitis, hypersensitivity pneumonitis, allergicbronchopulmonary mycosis, emphysema, acute respiratory distresssyndrome, asthma, bronchitis, chronic obstructive pulmonary disease,chronic bronchitis, pulmonary emphysema, diffuse panbronchiolitis,respiratory obstruction, graft versus host syndrome, urticaria,ultraviolet radiation dermatitis, atopic dermatitis, cancer, myelogenousleukemia, sarcomata, brain tumor, cachexia, tissue ulcer, digestiveulcer, gastritis, acute and chronic pancreatitis, regional enteritis,ulcerative colitis, diverticulitis, recurrent gastroenteric disorder,gastroenteric bleeding, inflammatory bowel disease, Crohn's disease,intestinal tract type Behcet's disease, infectious enteritis, ischemicenteritis, radiation enteritis, drug-induced enteritis, irritable bowelsyndrome, hepatic diseases (hepatopathies, liver failures) such as acutehepatitis, fulminant hepatitis, chronic hepatitis, hepatic cirrhosis,fatty liver, alcoholic liver injury, drug liver injury (drug-inducedhepatitis), congestive hepatitis, autoimmune hepatitis, primary biliarycirrhosis and hepatic porphyria, coagulation, anemia, ankylosingspondilitis, restenosis, periodontosis, epidermolysis bullosa,atherosclerosis, aortic aneurysm, periarteritis nodosa, congestivecardiac failure, arrhythmia, myocardial infarction, cerebral infarction,attack, cerebral ischemia, head injury, spinal cord injury, myelopathicmuscular atrophy, neuralgia, neurodegenerative disease, Alzheimer'sdisease, Lewy body disease, Shy-Drager syndrome, Reye's syndrome,progressive supranuclear palsy, progressive multifocalleukoencephalopathy, normal pressure hydrocephalus, subacute sclerosingpanencephalitis, frontal lobe type dementia, acute anteriorpoliomyelitis (poliomyelitis), poliomyelitis neurosis, viralencephalitis, Creutzfeldt-Jakob disease, Kuru disease, bovine spongiformencephalopathy (mad cow disease), scrapie, epilepsy, cerebral amyloidangiopathy, autoimmune disease, Huntington's disease, Parkinson'sdisease, migraine, depression, mania, manic-depressive psychosis,hereditary cerebellar ataxia, peripheral neuropathy, glaucoma, pain,gingivitis, postoperative pain, amyotrophic lateral sclerosis,osteoporosis, multiple sclerosis, ocular angiogenesis, cornea damage,macular degeneration, conjunctivitis, abnormal wound healing, sprain orstrain of muscle or joint, tendinitis, skin disease, psoriasis vulgaris,pustular psoriasis, erythroderma psoriaticum, arthritic psoriasis,myasthenia gravis, multiple myositis, myositis, bursitis, diabetesmellitus, tumor invasion, tumor growth, tumor metastasis, cornea scar,scleritis, immunodeficiency disease, pachydermia, eosinophilicfasciitis, sepsis, endotoxin shock, premature delivery,hypoprothrombinemia, hemophilia, thyroiditis, sarcoidosis, Behcet'ssyndrome, hypersensitivity, renal disease, rickettsial infectiousdisease, protozoal disease, reproduction disease, sepsis shock and thelike. Other specific conditions and diseases include toothache, painafter tooth extraction, back or low back pain, periarthritishumeroscapularis, cervico-omo-brachial syndrome, tenosynovitis, acuteupper respiratory inflammation, herpes zoster, fibrosis, pulmonaryfibrosis, pneumoconiosis, chronic interstitial pneumonia, granulomatousinterstitial pneumonia, fibrosing interstitial pneumonia, renalfibrosis, nephropyelitis, various types of secondary contracted kidney,glomerular nephritis, chronic nephritis, glomerulosclerosis, hepaticfibrosis, cardiac fibrosis after myocardial infarction, idiopathiccardiomyopathy, pancreatic sclerosis, pancreatic fibrosis,pancreatolithiasis, Takayasu's arteritis, chronic thyroiditis,dermatomyositis, multiple myositis, myelofibrosis, Banti disease,retroperitoneal fibrosis, various radiation injuries and the like.Further, the medicament comprising Compound (I) of the present inventionas an active ingredient can be used for the aforementioned conditions ordiseases of mammals, preferably humans, pets or companion animals suchas dogs and cats or farm animals together with or in combination withone or more kinds of other prophylactic or therapeutic drugs.

Examples of the drugs that can be used together or in combinationinclude, for example, the following drugs: immunomodulation-typeantirheumatic drugs and antimetabolite used as therapeutic drugs forrheumatoid arthritis, specifically, gold preparations, bucillamine,lobenzarit, salazosulfapyridine, methotrexate, azathiopurin, mizoribine,leflunomide, tacrolimus, cyclosporin and the like and preparationscontaining the same; anti-cytokine antibody preparations directed tocytokines such as interleukin (IL) 1, IL-6, and tumor necrosis factor(TNF)-α or preparations of soluble receptors for those cytokines, whichare biological preparations, specifically, infliximab, etanercept andthe like and preparations containing the same; steroid preparations,specifically, dexamethasone, betamethasone, prednisolone, fluticasone,beclometasone and the like and preparations containing the same;bronchodilators used as therapeutic agents for chronic bronchial asthma,specifically, salmeterol and salbutamol, which are adrenalin β2stimulants, ipratropium, which is an anticholinergic drug, and the likeand preparations containing the same; therapeutic drugs for allergicdiseases, for example, theophyline, which is a xanthine analogue drug,and the like, fexoquinadine, epinastatine, cetirizine, ketotifen,disodium cromoglycate, pemirolast and the like, which are antiallergicagents, fexoquinadine, cetirizine and the like, which are antihistaminicagents, and preparations containing the same; irinotecan, 5-fluorouraciland the like, which are antitumor agents, and preparations containingthe same. Further, the medicament comprising Compound (I) of the presentinvention as an active ingredient is used, for example, together with orin combination with radiotherapy.

In order to use Compound (I) of the present invention orpharmaceutically acceptable salts thereof for the medicaments describedabove, an effective amount of Compound (I) of the present invention or apharmaceutically acceptable salt thereof, per se, may be used, or thesubstance may be mixed with a pharmaceutically acceptable carrier toform a pharmaceutical composition. The carrier may be, for example, asuspending agent such as carboxymethylcellulose, or purified water,physiological saline or the like, if desired. Other known carriers canalso be used. Examples include a method of dissolving Compound (I) ofthe present invention or a pharmaceutically acceptable salt thereof inpurified water containing 0.5% carboxymethylcellulose and using thesolution.

Examples of formulations for preparing the aforementioned pharmaceuticalcomposition include tablet, powder, granule, syrup, suspension, capsule,and injection. For the manufacture of these formulations, variouscarriers suitable for these preparations are used. For example, examplesof the carrier for oral preparations include excipients, binders,lubricants, fluid accelerators, and colorants.

When the compound of the present invention is formulated as a parenteralpreparation such as an injection, water for injection, physiologicalsaline, glucose aqueous solution, vegetable oil for injection, propyleneglycol, polyethylene glycol and the like can generally be used as adiluent. Disinfectants, antiseptics, stabilizers, isotonic agents,soothing agents and the like may be further added, as required.

When the compound of the present invention is administered to a mammal,e.g., human, the compound can be administered in the form of a tablet, apowder, a granule, a suspension, a capsule or the like. The compound canalso be parenterally administered in the form of a suppository, a gel, alotion, an ointment, a cream, or a spray. A dose thereof variesdepending on a disease to be applied, administration route, age, weight,degree of symptom of a patient and the like. Examples of the doseinclude generally an administration at a dose of 1 to 1,000 mg per dayfor an adult once to three times a day. Every day administration for aperiod of several days to two months is commonly applied. The daily doseand the administration period may be increased or decreased depending onsymptoms of a patient.

Fibrosis, which is a disease characterized by fibrosing of tissues, isknown as a severe disease which is often mortal. Fibrosing of tissues iscaused by proliferation of interstitial cells, which represented byfibroblasts, and production of extracellular matrix such as collagen.Fibrosing is considered a repair mechanism against tissue affections inorgans. Excessive fibrosing causes fibrosing diseases of organs, andfurther progression of fibrosing causes sclerotic diseases. Many of suchsclerotic diseases are intractable, progressive and irreversible.Although fibrosing varies in various organs, etiological hypotheses offibrosing have many similarities. That is, a certain inflammatory lesionprecedes, and in its healing process, various kinds of cytokines andgrowth factors are produced mainly from immunocompetent cells andplatelets as well as interstitial cells such as fibroblasts themselvesinvolved in the healing, and activated to cause deposition ofextracellular matrix (Takehara, Molecular Medicine, 2001, vol 38, p.854).

Among fibroses, pulmonary fibrosis is one of the representativediseases. Pulmonary fibrosis is a disease in which disruption ofalveolar structure is caused by chronic inflammation and increase ofcollagenic fibers in alveolar walls, and which eventually leads torespiratory failure and death. For example, pulmonary fibrosis occursfollowing infectious pneumonia and the like. Examples of the infectiouspneumonia include severe acute respiratory syndrome (SARS) andinfluenzal pneumonia. It has been reported that, in SARS, in particular,severe inflammation is caused in pulmonary stroma, and as a result, ithighly likely to develop into pulmonary fibrosis (Antonino et al.,Radiology, 2003). In addition, pulmonary fibrosis is also caused byvarious medicaments.

In recent years, with increase of medicaments used for diagnosis,prophylactic and therapeutic treatments of various kinds of diseases,drug-induced pulmonary fibrosis caused by such drugs is increasing.Drug-induced pulmonary fibrosis is a severe disease that eventuallyleads to death, and it causes serious problems in therapeutic treatmentsof various diseases. Therefore, prophylactic and therapeutic treatmentsof drug-induced pulmonary fibrosis constitute a particularly importantsubject of concern.

Against drug-induced pulmonary fibrosis, steroid therapy is currentlyused. However, effective rate of the steroid therapy is low and theeffect is only partial and transient, and thus lesions often remain[Igaku no Ayumi, 2001, vol. 197, p. 313]. Further, side effect ofsteroid agents and acute aggravation due to decrease of doses ortermination of their administrations are also often observed, whichremains clinically far unsatisfactory level.

As a recent finding, it was reported that administration of pirfenidonewas effective against pulmonary fibrosis in clinical tests in the UnitedStates (Raghu et al., American Journal of Respiratory and Critical CareMedicine, 1999, vol. 159, p. 1061) and Japan (Nagai et al., InternalMedicine, 2002, vol. 41, p. 1118). However, development of novelprophylactic and/or therapeutic agents highly effective for thesediseases is desired at all events.

The medicament provided by the present invention is useful as amedicament containing a type 4 PLA₂ inhibitor as an active ingredientfor prophylactic and/or therapeutic treatment of fibrosis, preferablypulmonary fibrosis, further preferably drug-induced pulmonary fibrosis.

As described above, fibrosis, in particular, pulmonary fibrosis, is asevere disease and is an important object of prophylactic and/ortherapeutic treatment. As for pulmonary fibrosis, more than 100 kinds offactors including toxic gases and various medicaments have beenelucidated as the causes of early alveolopathy. As described above, withthe increase of medicaments used for diagnosis, prophylactic andtherapeutic treatments of various kinds of diseases, drug-inducedpulmonary fibrosis caused by such drugs is increasing.

As for drug-induced pulmonary fibrosis, causality between expression ofpathological conditions such as coughing, difficulty of breathing, orfervescence and the administration of medicaments is suspected, and itis considered that a diffuse interstitial shadow appears on a thoracicX-ray photograph simultaneously with or slightly after theadministration of medicaments.

As medicaments reported to cause drug-induced pulmonary fibrosis,anticancer agents, anti-rheumatic agents, immunosuppressants,antibiotics, chemotherapeutants, antihypertensive agents, diuretics,anti-inflammatory/analgesic agents, biologics, Chinese medicines areknown (Inooka et al., Therapeutics, 1995, vol. 29, p. 1295). Typicalmedicaments are shown in Table 1.

TABLE 1 Classification Examples of agent 1) Anticancer agent,Peplomycin, bleomycin, cychlophosphamide, nitrosourea, immunosuppressantbusulfan, methotrexate, azathioprine, mitomycin-C, tegafur, carmofur,tegafur/uracil preparation, cisplatin, doxorubicin, 6-mercaptopurine,daunomycin, vincristine, vinblastine, vindesine, procarbazine,neocarzinostatin, melphalan, thiotepa, nimustine, cytarabine, zinostatinstimalamer, chlorambucil, carmustine, lomustine, semustine, teniposide,etoposide, Taxol, taxotere, irinotecan, gefitinib, tamoxifen and thelike. 2) Antihypertensive α-methyldopa, trichlormethiazide,hydrochlorothiazide, agent, diuretic enalapril, hexamethonium,mecamylamine, pentolinium, practolol, pindolol, propranolol, acebutolol,hydralazine 3) Antibiotic, Cephem antibiotics (cephaloridine,cephalothin, chemotherapeutant cephalexin, cefradine, cefazolin,cefaclor, cefmenoxime, cefmetazole, cefoperazone, cefotiam, cefroxadin,ceftizoxime, latamoxef and the like), tetracyclines (minocycline,oxycycline), antituberculous agents (isoniazid, paraaminosalicylic acid,rifampicin, streptomycin), penicillin antibiotics (ampicillin,piperacillin, vastcillin, pentcillin, amoxicillin), aminoglycosideantibiotics (streptomycin), macrolide antibiotics (midecamycin),phosphomycin, aminoglycosides (tobramycin, Micromycin), new quinolonedrugs (enoxacin, ofloxacin, norfloxacin), antifungal agents(amphotericin) and the like 4) Others Inhalants (cromoglicic acid andthe like), gold preparations (aurothiomalic acid and the like),psychotropic agents and nervines (aminotriptyline, diphenylhydantoin,carbamazepine, phenobarbital, valproate salt, imipramine, mephenesin,meprobamate), antiphlogistic and analgesics (naproxen, acetaminophen,acetylsalicylic acid, phenacetin, diclofenac, loxoprofen, fenbufen,nabumetone, aluminoprophen and the like), antiarrhythmic agents(amiodarone, procainamide, aprindine), antidiabetic agents(chlorpropamide), antithyroid agents (thiouracil), proteolytic enzymes(serrapeptidase), antiparkinsonic agents (levodopa, bromocriptine),antirheumatic agents (bucillamine, auranofin, actarit), sho-saiko-to,chai-ling-tang, rikkunshi-to, interferon, warfarin, salazosulfapyridine,dichloroferamide, fominoben, D-penicillamine, propylthiouracil,corticosteroid, flavoxate, allopurinol, ethoxysclerol and the like

In therapeutic treatment of rheumatoid arthritis, for example, agentsthat cause pulmonary fibrosis at high frequency such as methotrexate andsodium aurothiomalate are used as disease-modifying antirheumatic drugs.Further, disease-modifying antirheumatic drugs that may cause pulmonaryfibrosis at a relatively low frequency, such as actarit, bucillamine,auranofin, salazosulfapyridine, and D-penicillamine are also used.Although these disease-modifying antirheumatic drugs are useful agent inthe rheumatoid arthritis treatment system, pulmonary fibrosis caused asa side effect is a factor of restricting use of these drugs. In recentyears, methotrexate, in particular, has come to be used as anantirheumatic agent, and onset of pulmonary fibrosis that is alsohistopathologically called interstitial pneumonia as the side effect ofmethotrexate becomes a problem in the rheumatoid arthritis treatmentsystem.

Further, in cancer therapy, cychlophosphamide, Taxol, etoposide,cisplatin, vincristine, vinblastine, irinotecan, gefitinib, andbleomycin are useful as anticancer agents. However, because all of theseanticancer agents cause pulmonary fibrosis that is alsohistopathologically called as interstitial pneumonia as a side effect ata high frequency, they have a problem in the therapeutic treatmentsystem. Bleomycin, gefitinib, irinotecan, and cisplatin are used fortherapeutic treatment of lung cancer. However, if patients with lungcancer develop pulmonary fibrosis, the condition is most likely for thepatients to be fatal. Among these drugs, bleomycin suffers from aproblem that it causes pulmonary fibrosis at a high frequency.

Preferred objects of application of the medicament of present inventionare drug-induced pulmonary fibroses caused by these drugs.

In present invention, the type 4 PLA₂ inhibitor is not particularlylimited so long as the inhibitor has type 4 PLA₂ inhibitory activity.For example, known type 4 PLA₂ inhibitors can be chosen. Examples of theknown type 4 PLA₂ inhibitors include the following inhibitors: thecompounds described in U.S. Pat. No. 5,462,954, preferably2-phenyl-4-ethyl-5-[6-(2H-tetrazol-5-yl)-6-methylheptyloxy]phenol,8-propyl-7-{3-[4-(4-fluorophenyl)-2-ethyl-5-hydroxyphenyloxy]propyloxy}-3,4-dihydro-2H-1-benzopyran-2-carboxylicacid, and2-{3-[3-([5-ethyl-2-hydroxy(1,1′-biphenyl)-4-yl]oxy)propyloxy]-2-propylphenyloxy}propionicacid; the compounds described in WO99/43654, preferably4-(1-benzhydryl-6-chloro-1H-indol-3-ylmethyl)-3-methoxybenzoic acid; thecompounds described in WO98/33797, preferablyN-{4-(biphenyl-2-ylmethyl-isobutylamino)-1-[2-(4-fluorobenzoyl)benzoyl]pyrrolidin-2-ylmethyl}-3-[4-(2,4-dioxothiazolidin-5-ylidenemethyl)phenyl]acrylamideand the like; the compounds described in WO01/30387, preferablyN-{1-[2-(2,4-difluorobenzoyl)benzoyl]-4-tritylsulfanylpyrrolidin-2-ylmethyl}-4-(2,4-dioxothiazolidin-5-ylidenemethyl)benzoicacid amide and the like; the compounds described in WO99/15129,preferably4-{4-[2-(2-[bis(4-chlorophenyl)methoxy]ethylsulfonyl)ethoxy]phenyl}-1,1,1-trifluoro-2-butanoneand the like; the compounds described in WO98/05637, preferably1-{2-[4-(carboxymethyl)phenoxy]ethyl}-3-dodecanoylindole-2-carboxylicacid and the like; the compounds described in Japanese Patent UnexaminedPublication (Kokai) No. 2002-80368, preferably4-methyl-2-oxo-5-(5,6,7,8-tetrahydronaphthalen-2-yl)oxazolidine-3-carboxylicacid (6-methoxytetrahydropyran-2-yl)amide,4-methyl-2-oxo-5-(4-methylphenyl)thiazolidine-3-carboxylic acid(tetrahydropyran-2-yl)amide and the like; and the type 4 PLA₂ inhibitorsselected from the compounds described in WO98/08818, the compoundsdescribed in WO99/43651, the compounds described in WO99/43672, thecompounds described in WO03/048122, the compounds described inWO95/10508, the compounds described in WO97/05135, the compoundsdescribed in Japanese Patent Unexamined Publication No. 7-126166, thecompounds described in Japanese Patent Unexamined Publication No.7-224076, the compounds described in Japanese Patent UnexaminedPublication No. 7-224076, the compounds described in Japanese PatentUnexamined Publication No. 2000-119292, the compounds described inJapanese Patent Unexamined Publication No. 2000-109432, the compoundsdescribed in Japanese Patent Unexamined Publication No. 7-223997, thecompounds described in the U.S. Pat. No. 5,994,398, the compoundsdescribed in WO00/27824, the compounds described in Japanese PatentUnexamined Publication No. 2000-38380, the compounds described inWO00/71118, the compounds described in Japanese Patent No. 3107613, thecompounds described in WO03/031414, the compounds described in U.S. Pat.No. 5,453,443, and the compounds described in WO02/038575. Examplesfurther include the following known type 4 PLA₂ inhibitors described inreferences: arachidonyl trifluoromethyl ketone (Street et al.,Biochemistry, 1993, vol. 32, p. 5935); methyl arachidonylfluorophosphate (Kennedy et al., Mediators of Inflammation, 1994, vol.3, p. 337); β-lactam derivatives (Burke et al., J. Enzyme Inhibition,1998, vol. 13, p. 195); choline derivatives (Burke et al., J. Biol.Chem., 1999, Vol. 274, p. 18864); 1,3-disubstituted propan-2-onederivatives, especially4-[3-(4-decyloxyphenyloxy)-2-oxopropyloxy]benzoic acid (Connolly et al.,J. Med. Chem., 2002, vol. 45, p. 1348); Surfactin (Kim et al., Biochem.Pharmacol., 1998, vol. 55, p. 975);1,1,1-trifluorononadeca-10,13,16-trien-2-one and1,1,1-trifluorononadeca-10,13-dien-2-one (Amandi-Burgermeister et al.,Eur. J. Pharmacol., 1997, vol. 326, p. 237); and 2-oxoamide derivatives(Kokotos et al., J. Med. Chem., 2002, vol. 45, p. 2891).

In the present invention, preferred examples of type 4 PLA₂ inhibitorfurther include the compounds represented by the aforementioned formula(I) and pharmacologically acceptable salts thereof. Various combinationsof the compounds represented by the formula (I) and pharmacologicallyacceptable salts thereof described in the specification can also bearbitrarily chosen.

When a medicament comprising a type 4 PLA₂ inhibitor as an activeingredient is used as a prophylactic and/or therapeutic agent forfibrosis, as for Compound (I) of the present invention, for example,Compound (I) of the present invention or a pharmaceutically acceptablesalt thereof, per se, may be used in an effective amount, or thesubstance may be used after preparation of a pharmaceutical compositionin the form of solid, liquid or gel by mixing the substance with apharmaceutically acceptable carrier. As for the pharmaceuticallyacceptable carrier, known information and the information about carriersdescribed in this specification can be referred to. As for known type 4PLA₂ inhibitors, a known type 4 PLA₂ inhibitor or a pharmaceuticallyacceptable salt thereof, per se, may be used in an effective amount, oras mentioned above, the inhibitors may be used after preparation of apharmaceutical composition by mixing the inhibitor with apharmaceutically acceptable carrier.

It would be readily understood by those skilled in the art thatprogression-preventing agents, that is used for preventing progressionof pathological conditions, occasionally fall within the scope of theagent for prophylactic and/or therapeutic treatment of the presentinvention.

Examples of the dosage form for preparation of the aforementionedpharmaceutical composition, tablet, powder, granule, syrup, suspension,capsule, inhalant, injection, and the like, and in order to prepare thecompositions, various carriers are used depending on the type of thecomposition. Examples of the carrier for oral agents include, forexample, excipients, binders, lubricants, flowability improvers, andcolorants. When an inhalant is prepared (examples of administrationmethod include a method of inhaling powder of the pharmaceuticalcomposition or a solution obtained by dissolving or suspending thepharmaceutical composition in a solvent, per se, a method of inhalingmist of the composition prepared by using a sprayer called atomizer ornebulizer), the preparation the aforementioned pharmaceuticalcomposition in the form of solid can be referred to for preparation of apowder for the inhalation, and a powder obtained is preferably furthermade into micropowder. When the composition is inhaled as a liquid,preferred examples of the preparation method include a method ofdissolving a solid pharmaceutical composition, which is prepared byreferring to the above explanation, in distilled water or a suitablesolvent to obtain a solution of medicament upon use, and a method ofpreparing a liquid pharmaceutical composition prepared by referring theabove explanation to obtain a solution of medicament. As for a size ofthe aforementioned powder or mist of a solution of a medicament to beinhaled, a particle size may be suitable for inhalation. For example, anupper limit is preferably 100 μm or less, further preferably 50 μm orless, most preferably 10 μm or less. A lower limit is not particularlylimited, and a smaller particle size is more preferred. When aninjection and the like are prepared, distilled water for injection,physiological saline, glucose solution, vegetable oil for injection,propylene glycol, polyethylene glycols and the like can generally beused as diluents. Further, antimicrobial agents, antiseptics,stabilizers, isotonic agents, soothing agents, and the like may beadded, as required.

When the aforementioned prophylactic and/or therapeutic agent isadministered, a suitable dosage form can be chosen and administered viaa suitable route. For example, the agent can be orally administered inthe form of a tablet, a powder, a granule, a syrup, a suspension, or acapsule. The agent can also be administered via transairway route in theform of an inhalant. Further, the agent can be administeredsubcutaneously, intradermally, intravascularly, intramuscularly orintraperitoneally in the form of injection including a drip infusion.Furthermore, the agent can be transmucosally administered in the form ofa sublingual agent or a suppository, and can be transdermallyadministered in the form of a gel, a lotion, an ointment, a cream, or aspray.

A dose thereof varies depending on the dosage form, and the age, weight,degree of symptoms of a patient and the like. Examples of the doseinclude generally an administration at a dose of 1 to 1,000 mg per dayfor an adult once to three times a day. Every day administration for aperiod of several days to two months is commonly applied. The daily doseand the administration period may be increased or decreased depending onsymptoms of a patient.

As for the application of the aforementioned prophylactic and/ortherapeutic agent, the agent may be administered to patients withpulmonary fibrosis as explained above. In addition, the prophylacticand/or therapeutic agent of the present invention containing a type PLA₂inhibitor as an active ingredient may preferably be administered afterthe administration of, most preferably immediately after theadministration of an agent, which may possibly induces pulmonaryfibrosis as an adverse reaction. Furthermore, as for the administrationtime, the prophylactic and/or therapeutic agent of the present inventionmay be administered simultaneously with an agent which may possiblyinduces pulmonary fibrosis as an adverse reaction, or the agent of thepresent invention may be administered beforehand.

EXAMPLES

The present invention will be further specifically explained withreference to examples. However, the scope of the present invention isnot limited to the following examples. In the examples, for thin layerchromatography (TLC), Precoated Silica Gel 60 F254 (produced by Merck,product number: 5715-1M)) was used. After development withchloroform:methanol (1:0 to 1:1), acetonitrile:acetic acid:water(200:1:1 to 100:4:4) or ethyl acetate:hexane (1:0 to 0:1), spots wereobserved by UV irradiation (254 nm) or color development with ninhydrineor dinitrophenylhydrazine solution in hydrochloric acid. For dryingorganic solvent, anhydrous magnesium sulfate or anhydrous sodium sulfatewas used. As for column chromatography, the indication of “Quad” meansuse of Quad 1 preparative chromatography system (produced by Biotage),and one or several columns selected from cartridge columns KP-Sil-12M,40S and 40M produced by the same manufacturer were used depending on theamount of sample. For flash column chromatography, Silica gel 60N(spherical shape, neutral, 40 to 100 μm, produced by Kanto Chemicals)was used. Preparative thin layer chromatography (hereinafter abbreviatedas “PTLC”) was performed by using one or several plates of PLC PlateSilica Gel 60 F254 (20×20 cm, thickness: 2 mm, concentration zone: 4 cm,produced by Merck, product number: 13793-1M) were used depending on theamount of sample.

The indication of “LCMS” means that mass spectrum was measured by liquidchromatography-mass spectrometry (LC-MS). Platform-LC type massspectrometry apparatus (produced by Micromass) was used as the massspectrometer, and the measurement was performed by the electrosprayionization (ESI) method. As a liquid chromatography apparatus, anapparatus produced by GILSON was used. As a separation column, MightysilRP-18 GP 50-4.6 (produced by Kanto Chemicals) was used. Elution wasgenerally performed at a flow rate of 2 ml/minute, and Solution A=water[containing 0.1% (v/v) acetic acid] and Solution B=acetonitrile[containing 0.1% (v/v) acetic acid] were used as solvents.

In the tables mentioned below, data indicated by “LCMS” mean data ofliquid chromatography-mass spectrometry spectra. In the columns of“Mass”, data of mass spectrometry were shown (the indication “N.D” meansthat no molecular ion peak was detected). In the columns of “method”,elution conditions of the liquid chromatography are described. In thecolumns of “RTime”, retention times in the liquid chromatography areshown. For the indication of retention time in the liquidchromatography, the indication “A” for elution condition means thatmeasurement was performed by elution with a linear gradient of 5 to 100%(v/v) Solution B from 0 minute to 5 minutes and then with 100% SolutionB until 6 minutes. Similarly, the indication “B” for elution conditionmeans that measurement was performed by elution with 30% (v/v) SolutionB from 0 minute to 0.5 minute, then with a linear gradient of 30 to 95%(v/v) Solution B from 0.5 minute to 4 minutes and then with 95% (v/v)Solution B until 6 minutes. For the compounds with the indication C inthe columns of elution conditions, data of mass spectrometry measured byfast atomic bombardment mass spectrometry (FAB-MS) using JEOL-JMS-SX102(produced by JEOL Co., Ltd.) were mentioned in the columns of “Mass”.Further, for the compounds with the indication D in the elutionconditions, an apparatus manufactured by Waters Ltd. was used as aliquid chromatography apparatus. As a column for separation, DevelosilC³⁰-UG-5 (50×4.6 mm, Nomura Kagaku Co., Ltd.) was used. Measurement wasperformed under elution condition with a linear gradient of 5 to 98%(v/v) Solution B from 0 minute to 4 minutes and then with 100% SolutionB until 6 minutes.

In the columns indicated as “Exp.”, compound numbers are shown. When thetables include a column indicated as “position”, substituting positionsof substituents are indicated in the column. The abbreviations used inthe tables have the following meanings.

n: normal, i: iso, s: secondary, t: tertiary, c: cyclo, D: di, Me:methyl, Et: ethyl, Pr: propyl, Bu: butyl, Pen: pentyl, Hex: hexyl, Hep:heptyl, Ph: phenyl, Bn: benzyl, Py: pyridyl, Indan: indanyl, Ac: acetyl,CHO: formyl, COOH: carboxyl, NO2: nitro, DMA: dimethylamino, NH2: amino,CF3: trifluoromethyl, F: fluoro, Cl: chloro, Br: bromo, OMe: methoxy,OH: hydroxy, TFA: trifluoroacetyl, SO₂: sulfonyl, CO: carbonyl, Nap:naphthyl, Ind: 1H-indolyl, 1HIdz: 1H-indazolyl, 2HIdz: 2H-indazolyl,Bzt: benzothiazole, 2ABzt: 2-aminobenzothiazole, BF: benzofuranyl, BT:benzo[b]thienyl, Qu: Quinolyl, IQ: isoquinolyl

The numbers given before the substituents indicate substitutingpositions. The numbers given with hyphens before abbreviations ofaromatic rings indicate substituting positions of the aromatic rings.(S) indicates optically active substances with S-configuration, and (R)indicates optically active substances with R-configuration.Representative examples of the substituents shown in the tables withabbreviations are listed in Table 2 mentioned below.

TABLE 2 Structure abbreviation

cPenMeO

cHexMeO

iBuO

2EtBuO

2,3DMeBuO

cPenO

cHexO

cHepO

BnO

(R)1PhEtO

2ClBnO

4FBnO

2-IndanO

2(4FPh)EtO

2(4DMAPh)EtO

2(3-Py)EtO

2(PhO)EtO

3F,4(OMe)BnO

2-Nap

1-Nap

5-Ind

1Me-5-Ind

5-1HIdz

1Me-5-1HIdz

5-Bzt

5-2ABzt

2Me-5-Bzt

5-BT

5-BF

3-Qu

6-IQ

The manufacturers of the regents used may sometimes be indicated withthe following abbreviations.

TCI: Tokyo Kasei Kogyo Co., Ltd., Ald: Aldrich Co., KANTO: Kanto Kagaku,WAKO: Wako Pure Chemical Industries, Ltd., LANC: Lancaster Synthesis,MAYB: Maybridge, plc. Example A-1 Synthesis of methyl3-(4-hydroxyphenyl)propionate (Intermediate 1)

A solution obtained beforehand by adding thionyl chloride (18.3 ml,WAKO) dropwise to methanol (250 ml) and mixing the mixture under icecooling was added dropwise with a solution of3-(4-hydroxyphenyl)propionic acid (16.6 g, TCI) in methanol (50 ml)under ice cooling, stirred for 30 minutes, warmed to room temperature,and further stirred for 1.5 hours. The reaction mixture was concentratedunder reduced pressure, and then extracted with diethyl ether (200 ml).The organic layer was washed successively with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride and saturatedbrine. The organic layer was dried, and then the solvent was evaporatedunder reduced pressure to obtain the title compound (Intermediate 1,17.95 g).

Synthesis of methyl 3-(4-cyclopentylmethyloxyphenyl)propionate(Intermediate 2)

A solution of cyclopentane methanol (4.05 ml, Ald) in anhydroustetrahydrofuran (abbreviated as “THF” hereinafter, 40 ml) was added withtriethylamine (6.49 ml, WAKO), added dropwise with methanesulfonylchloride (3.48 ml, WAKO) under ice cooling, and stirred for 30 minutes.The reaction mixture was added with water (50 ml), and extracted withdiethyl ether (80 ml×2). The organic layer was washed with saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. A solution obtained beforehand by adding 60% sodium hydride(1.15 g, KANTO) to a solution of Intermediate 1 (4.50 g) inN,N-dimethylformamide (abbreviated as “DMF” hereinafter, 35 ml) underice cooling and stirring the solution for 15 minutes was added with asolution of the aforementioned residue in DMF (10 ml) under ice cooling.The reaction mixture was stirred for 15 minutes, then warmed to roomtemperature, stirred for 45 minutes, and further stirred at 60° C. for15 hours. The reaction mixture was added with water (100 ml) and diethylether (200 ml) for extraction. The organic layer was successively washedwith saturated aqueous sodium hydrogencarbonate, saturated aqueousammonium chloride, and saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:isopropyl ether=9:1) to obtain the titlecompound (Intermediate 2, 5.58 g).

Synthesis of methyl 3-(3-bromo-4-cyclopentylmethyloxyphenyl)propionate(Compound No. A-1)

A solution of Intermediate 2 (1.31 g) in acetonitrile (50 ml) was addedwith N-bromosuccinimide (hereinafter abbreviated as “NBS”, 979 mg,KANTO), stirred at room temperature for 2 hours, then warmed to 40° C.,and stirred for 3 hours. The reaction mixture was concentrated underreduced pressure, then added with ethyl acetate (200 ml) and washedsuccessively with saturated aqueous ammonium chloride, 5% aqueous sodiumsulfite, saturated aqueous sodium hydrogencarbonate and saturated brine.The organic layer was dried, and then the solvent was evaporated underreduced pressure to obtain the title compound (Compound No. A-1, 1.69g).

Example A-2 Synthesis of 3-(3-bromo-4-methoxyphenyl)propionic acid(Intermediate 3)

According to the procedure described in the synthesis method of CompoundNo. A-1 provided that the reaction was carried out under ice cooling for30 minutes and at room temperature for 3 hours,3-(4-methoxyphenyl)propionic acid (27.0 g, TCI) and NBS (29.4 g) werereacted and treated to obtain the title compound (Intermediate 3, 38.1g).

Synthesis of 3-(3-bromo-4-hydroxyphenyl)propionic acid (Intermediate 4)

According to a procedure described in a literature (Carreno, M. C., J.Org. Chem., 1995, vol. 60, p. 5328), a 1 M solution of boron tribromidein methylene chloride (200 ml, Fluka) was added dropwise with a solutionof Intermediate 4 (23.5 g) in methylene chloride (200 ml) at −78° C.,warmed to room temperature after 30 minutes, and further stirred for 1.5hours. The reaction mixture was poured into ice water (750 ml), andstirred at room temperature for 1 hour. The reaction mixture was addedwith diethyl ether (750 ml)) for extraction. The organic layer was addedwith 2 N aqueous sodium hydroxide (250 ml×2) for extraction, and thenthe aqueous layer was made acidic with 5 N aqueous hydrochloric acidunder ice cooling, and extracted with diethyl ether (375 ml×2) again.The organic layer was washed with saturated brine and dried, and thenthe solvent was evaporated under reduced pressure. The organic layer waswashed with saturated brine and dried, and then the solvent wasevaporated under reduced pressure to obtain the title compound(Intermediate 4, 23.5 g).

Synthesis of methyl 3-(3-bromo-4-hydroxyphenyl)propionate (Intermediate5)

According to the procedure described in the synthesis method ofIntermediate 1 provided that the purification was performed by flashcolumn chromatography (hexane:ethyl acetate=4:1), Intermediate 4 (21.15g) and thionyl chloride (15.0 ml) were reacted and treated in methanolto obtain the title compound (Intermediate 5, 20.36 g).

Synthesis of methyl (3-bromo-4-cyclohexylmethyloxyphenyl)propionate(Compound No. A-2)

A solution of Intermediate 5 (1.29 g) in DMF (25 ml) was added withpotassium carbonate (0.86 g) and bromomethylcyclohexane (1.05 ml, TCI),stirred under argon atmosphere at room temperature for 2 hours, thenwarmed to 60° C., and stirred for 17 hours. The reaction mixture waspoured into ice water, and extracted with isopropyl ether (200 ml). Theorganic layer was successively washed with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride, and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by flash column chromatography(hexane:isopropyl ether=9:1) to obtain the title compound (Compound No.A-2, 1.45 g).

Example A-5 Synthesis of methyl3-(3-bromo-4-cyclopentyloxyphenyl)propionate (Compound No. A-5)

A solution of Intermediate 5 (4.50 g) in DMF (20 ml) was added with 60%sodium hydride (440 mg, KANTO) under ice cooling. The reaction mixturewas stirred for 10 minutes, then added with bromocyclopentane (1.61 ml,TCI), warmed to room temperature, stirred for 1.5 hours, then warmed to60° C., and further stirred for 16 hours. The reaction mixture was addedwith water (50 ml) and isopropyl ether (300 ml)) for extraction. Theorganic layer was successively washed with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride, and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by flash column chromatography(hexane:isopropyl ether 7:1) to obtain the title compound (Compound No.A-5, 2.50 g).

Example A-6 Synthesis of methyl3-(3-bromo-4-cyclohexyloxyphenyl)propionate (Compound No. A-6)

A solution of Intermediate 5 (2.06 g), triphenylphosphine (hereinafterabbreviated as “Ph₃P”, 6.28 g, WAKO) and cyclohexanol (2.53 ml, WAKO) inanhydrous THF (60 ml) was added dropwise with a 40% solution ofdiisopropylazodicarboxylic acid ester in toluene (hereinafterabbreviated as “40% DLAD”, 11.35 ml, WAKO) under ice cooling over 10minutes. The reaction mixture was stirred for 10 minutes, then warmed toroom temperature, and stirred for 18.5 hours. The reaction mixture wasadded with water (50 ml) and ethyl acetate (200 ml)) for extraction. Theorganic layer was successively washed with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:isopropyl ether=8:1) to obtain the title compound (Compound No.A-6, 2.35 g).

Example A-20 Synthesis of methyl 3-(3bromo-5-chloro-4-hydroxyphenyl)propionate (Intermediate 6)

A solution of Intermediate 5 (516 mg) in chloroform (5 ml) was addedwith sulfuryl chloride (177 μl), and stirred at room temperature for 21hours. The reaction mixture was poured into aqueous saturated sodiumhydrogencarbonate (20 ml), and extracted with ethyl acetate. The organiclayer was successively washed with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride, and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:ethyl acetate=10:1) to obtain the title compound (Intermediate 6,290 mg).

Synthesis of methyl3-(3-bromo-5-chloro-4-cyclopentylmethyloxyphenyl)propionate (CompoundNo. A-20)

According to the procedure described in the synthesis method of CompoundNo. A-6 provided that the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=30:1), Intermediate 6 (278mg), Ph₃P (747 mg), cyclopentane methanol (308 μl), and 40% DIAD (1.34ml) were reacted and treated to obtain the title compound (Compound No.A-20, 337 mg).

Example A-21 Synthesis of ethyl 3-(3-fluoro-4-methyloxyphenyl)acrylate(Intermediate 7)

A solution of 3-fluoro-4-methoxybenzaldehyde (2.20 g, Ald) in1,2-diethoxyethane (5 ml) was added with ethyl diethylphosphonoacetate(3.12 ml, TCI) and added with 60% sodium hydride (624 mg) under icecooling. After being stirred for 10 minutes, the reaction mixture waswarmed to room temperature, and stirred for 5 hours. The reactionmixture was added with ethyl acetate (90 ml), and washed successivelywith saturated aqueous sodium hydrogencarbonate, saturated aqueousammonium chloride and saturated brine. The organic layer was dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by flash column chromatography (Quad, hexane:ethylacetate=10:1) to obtain the title compound (Intermediate 7, 3.16 g).

Synthesis of ethyl 3-(3-fluoro-4-methoxyphenyl)propionate (Intermediate8)

A solution of Intermediate 7 (3.01 g) in ethyl acetate (50 ml) andmethanol (25 ml) was added with 10% palladium/carbon (300 mg, Merck),and stirred at room temperature for 2 hours under hydrogen atmosphere.The reaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure to obtain the title compound(Intermediate 8, 3.02 g).

Synthesis of 3-(3-fluoro-4-methoxyphenyl)propionic acid (Intermediate 9)

A solution of Intermediate 8 (2.97 g) in methanol (40.0 ml) was addedwith 2 N aqueous sodium hydroxide (15.0 ml) and stirred at 60° C. for 16hours. The reaction mixture was concentrated under reduced pressure,then made acidic with aqueous 5% hydrochloric acid under ice cooling,and extracted with ethyl acetate (200 ml). The organic layer was washedwith saturated brine and dried, and then the solvent was evaporatedunder reduced pressure to obtain the title compound (Intermediate 9,2.40 g).

Synthesis of 3-(3-fluoro-4-hydroxyphenyl)propionic acid (Intermediate10)

A pyridine/hydrochloric acid complex prepared by mixing pyridine (30 ml)and concentrated hydrochloric acid (30 ml) and heating the mixture at190° C. for 1 hour was added with Intermediate 9 (2.40 g) and stirred at190° C. for 1.5 hours. The reaction mixture was poured into 1 Nhydrochloric acid (100 ml) cooled with ice, and extracted with ethylacetate (200 ml). The organic layer was washed with saturated brine anddried, and then the solvent was evaporated under reduced pressure toobtain the title compound (Intermediate 10, 1.98 g).

Synthesis of methyl 3-(3-fluoro-4-hydroxyphenyl)propionate (Intermediate11)

According to the procedure described in the synthesis method ofIntermediate 1, Intermediate 10 (1.77 g) and thionyl chloride (1.65 ml)were reacted and treated in methanol to obtain the title compound(Intermediate 11, 1.85 g).

Synthesis of methyl 3-(3-bromo-5-fluoro-4-hydroxyphenyl)propionate(Intermediate 12)

According to the procedure described in the synthesis method of CompoundNo. A-1 with the modifications that the reaction was carried out for 2hours under ice cooling, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=10:1), Intermediate 11 (1.84g) and NBS (1.74 g) were reacted and treated to obtain the titlecompound (Intermediate 12, 1.74 g).

Synthesis of methyl3-(3-bromo-4-cyclopentylmethyloxy-5-fluorophenyl)propionate (CompoundNo. A-21)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for 22hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=50:1), Intermediate 11 (310 mg),tributylphosphine (hereinafter abbreviated as “^(n)Bu₃P”, 405 μl, WAKO)instead of Ph₃P, cyclopentane methanol (176 μl), andN,N,N′,N′-tetramethylazodicarboxamide (hereinafter abbreviated as“TMAD”, 279 mg, TCI) instead of 40% DIAD were reacted and treated toobtain the title compound (Compound No. A-21, 386 mg).

Example A-24 Synthesis of 4-cyclopentyloxy-3-methylbenzaldehyde(Intermediate 13)

According to the procedure described in the synthesis method of CompoundNo. A-2 with the modifications that the reaction was carried out for 16hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=9:1), 4-hydroxy-3-methylbenzaldehyde (283mg, TCI), potassium carbonate (578 mg) and bromocyclopentane (430 μl)were reacted and treated to obtain the title compound (Intermediate 13,350 mg).

Synthesis of ethyl 3-(4-cyclopentyl-3-methylphenyl)acrylate(Intermediate 14)

According to the procedure described in the synthesis method ofIntermediate 7 with the modifications that the reaction was carried outfor 2 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate==9:1), Intermediate 13 (342 mg), ethyldiethylphosphonoacetate (408 μl) and 60% sodium hydride (82 mg) werereacted and treated to obtain the title compound (Intermediate 14, 450mg).

Synthesis of ethyl 3-(4-cyclopentyl-3-methylphenyl)propionate(Intermediate 15)

According to the procedure described in the synthesis method ofIntermediate 8, Intermediate 14 (446 mg) and 10% palladium/carbon (20mg) were reacted and treated under hydrogen gas atmosphere to obtain thetitle compound (Intermediate 15, 439 mg).

Synthesis of ethyl 3-(3-bromo-4-cyclopentyl-5-methylphenyl)propionate(Compound No. A-24)

According to the procedure described in the synthesis method of CompoundNo. A-1, Intermediate 15 (437 mg) and NBS (320 mg) were reacted andtreated to obtain the title compound (Compound No. A-24, 545 mg).

Example A-251 Synthesis of3-bromo-4-(t-butyldimethylsilyloxy)-5-methoxybenzaldehyde (Intermediate16)

A solution of 3-bromovanillin (1.16 g, TCI) in anhydrous DMF (20 ml) wasadded with imidazole (408 mg, TCI), added dropwise with a solution of4-(N,N-dimethylamino)pyridine (25 mg) and t-butyldimethylsilyl chloride(904 mg, TCI) in DMF (15 ml) under ice cooling, stirred 30 minutes, thenwarmed to room temperature, and further stirred 3 hours. The reactionmixture was added with water (100 ml), and extracted with ethyl acetate(100 ml). The organic layer was washed with saturated brine and dried,and then the solvent was evaporated under reduced pressure. The residuewas purified by flash column chromatography (hexane:ethyl acetate=9:1)to obtain the title compound (Intermediate 16, 1.75 g).

Synthesis of ethyl3-[3-bromo-4-(t-butyldimethylsilyloxy)-5-methoxyphenyl]acrylate(Intermediate 17)

According to the procedure described in the synthesis method ofIntermediate 7 with the modifications that the reaction was carried outfor 1.5 hours, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=9:1), Intermediate 16 (910 mg),ethyl diethylphosphonoacetate (530 μl) and 60% sodium hydride (120 mg)were reacted and treated to obtain the title compound (Intermediate 17,937 mg).

Synthesis of ethyl3-[3-bromo-4-(t-butyldimethylsilyloxy)-5-methoxyphenyl]propionate(Intermediate 18)

According to the procedure described in the synthesis method ofIntermediate 8, Intermediate 17 (945 mg) and 10% palladium/carbon (95mg) were reacted and treated under hydrogen gas atmosphere to obtain thetitle compound (Intermediate 18, 760 mg).

Synthesis of ethyl 3-(3-bromo-4-hydroxy-5-methoxyphenyl)propionate(Intermediate 19)

A solution of Intermediate 18 (750 mg) in THF (50 ml) was added with a 1M solution of tetrabutylammonium fluoride in THF (5 ml, TCI), andstirred for 1.5 hours. The reaction mixture was added with saturatedaqueous sodium hydrogencarbonate (30 ml), and extracted with ethylacetate (50 ml). The organic layer was washed with saturated brine anddried, and then the solvent was evaporated under reduced pressure. Theresidue was purified by flash column chromatography (hexane:ethylacetate=4:1) to obtain the title compound (Intermediate 19, 542 mg).

Synthesis of ethyl3-(3-bromo-4-cyclopentyloxy-5-methoxyphenyl)propionate (Compound No.A-25)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for 16hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=7:1), Intermediate 19 (400 mg), Ph₃P (1.31g), cyclopentanol (450 μl), and TMAD (860 mg) were reacted and treatedto obtain the title compound (Compound No. A-25, 376 mg).

Example A-26 Synthesis of methyl3-(3-bromo-4-cyclopentylmethyloxy-5-nitrophenyl)propionate (Compound No.A-26)

A solution obtained beforehand by adding 70% nitric acid (3.9 ml) toacetic anhydride (30 ml) under ice cooling and stirring the mixture for10 minutes was added with a solution of Compound No. A-1 (5.12 g) inacetonitrile (25 ml) at −15° C. over 15 minutes, and stirred further for15 minutes. The reaction mixture was poured into 1 N aqueous sodiumhydroxide (500 ml) containing ice, and extracted with diethyl ether (300ml×2). The organic layer was successively washed with saturated aqueoussodium hydrogencarbonate, saturated aqueous ammonium chloride, andsaturated brine and dried, and then the solvent was evaporated underreduced pressure. The residue was purified by column chromatography(Quad, hexane:ethyl acetate=10:1) to obtain the title compound (CompoundNo. A-26, 3.68 g).

Example A-31 Synthesis of methyl 3-(3-bromo-4-phenoxyphenyl)propionate(Compound No. A-31)

A solution of Intermediate 5 (3.08 g) in anhydrous N-methylpyrrolidone(9.5 ml, WAKO) was successively added with cesium carbonate (3.58 g,WAKO), iodobenzene (1.4 ml, TCI), dipivaloylmethane (0.12 ml, TCI) andcopper(I) chloride (275 mg, WAKO), and stirred 120° C. for 16 hoursunder argon gas atmosphere. The reaction mixture was added with t-butylmethyl ether (25 ml), and insoluble solids were removed by filtration.The filtrate was washed successively with 2 N aqueous hydrochloric acidand saturated brine and dried, and then the solvent was evaporated underreduced pressure. The residue was purified by flash columnchromatography (hexane:ethyl acetate=1:10) to obtain the title compound(Compound No. A-31, 1.00 g).

Example B-96 Synthesis of methyl 3-(3-bromo-4-methoxyphenyl)propionate(Intermediate 20)

According to the procedure described in the synthesis method ofIntermediate 1 provided that the purification was performed by flashcolumn chromatography (hexane:ethyl acetate=6:1), Intermediate 3 (1.60g) and thionyl chloride (1.44 ml) were reacted and treated in methanolto obtain the title compound (Intermediate 20, 1.63 g).

Synthesis of methyl 3-(3-bromo-4-methoxy-5-nitrophenyl)propionate(Intermediate 21)

A solution of Intermediate 20 (3.20 g) in acetic anhydride (25 ml) wasadded with potassium nitrate (1.30 g) under ice cooling and stirred for10 minutes, and the solution was added dropwise with concentratedsulfuric acid (730 μl) over 10 minutes. The reaction mixture was stirredfor 10 minutes for 10 minutes at the same temperature, then warmed toroom temperature, and further stirred for 30 minutes. The reactionmixture was poured into 1 N aqueous sodium hydroxide (250 ml) containingice, and extracted with isopropyl ether (200 ml×2). The organic layerwas successively washed with saturated aqueous sodium hydrogencarbonate,saturated aqueous ammonium chloride, and saturated brine and dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by column chromatography (Quad, hexane:ethyl acetate=10:1) toobtain the title compound (Intermediate 21, 2.73 g).

Synthesis of 3-(3-bromo-4-methoxy-5-nitrophenyl)propionic acid(Intermediate 22)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 1 hour,Intermediate 21 (12.73 g) and 2 N aqueous sodium hydroxide (40 ml) werereacted and treated to obtain the title compound (Intermediate 22, 11.53g).

Synthesis of 3-(3-bromo-4-hydroxy-5-nitrophenyl)propionic acid(Intermediate 23)

According to the procedure described in the synthesis method ofIntermediate 4 provided that the reaction was carried out for 2 hours,Intermediate 22 (11.53 g) and a 1 M solution of boron tribromide inmethylene chloride (100 ml) were reacted and treated to obtain the titlecompound (Intermediate 23, 10.68 g).

Synthesis of methyl 3-(3-bromo-4-hydroxy-5-nitrophenyl)propionate(Intermediate 24)

According to the procedure described in the synthesis method ofIntermediate 1 provided that the reaction was carried out for 17.5hours, Intermediate 23 (10.68 g) and thionyl chloride (8.06 ml) werereacted and treated to obtain the title compound (Intermediate 24, 8.27g).

Synthesis of methyl3-[3-bromo-4-(indan-2-yloxy)-5-nitrophenyl]propionate (Compound No.B-96)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for 15hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=19:1), Intermediate 24 (151 mg), Ph₃P (260mg), 2-hydroxyindane (133 mg, TCI) and 40% DIAD (470 μl) were reactedand treated to obtain the title compound (Compound No. B-96, 192 mg).

Example B-99 Synthesis of methyl3-(3-amino-5-bromo-4-cyclopentyloxyphenyl)propionate (Compound No. B-99)

A solution of Compound No. A-28 (416 mg) in a mixture of THF (5 ml) andmethanol (5 ml) was added with Raney 2800 nickel (230 mg, Ald) andstirred at room temperature for 6 hours under hydrogen atmosphere. Thereaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate 5:2) to obtain the titlecompound (Compound No. B-99, 143 mg).

Example B-103 Synthesis of methyl3-[4-benzyloxy-5-bromo-3-(2,2,2-trifluoroacetylamino)phenyl]propionate(Compound No. B-103)

A solution of Compound No. B-100 (58.7 mg) in methylene chloride (2 ml)was added with triethylamine (76 μl), added dropwise trifluoroaceticanhydride (91 μl, TCI) under ice cooling, stirred for 30 minutes, thenwarmed to room temperature, and further stirred for 2 hours. Thereaction mixture was added with water (5 ml), and extracted withmethylene chloride (20 ml). The organic layer was washed with saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:ethyl acetate=3:1) to obtain the title compound (Compound No.B-103, 59.1 mg).

Example B-105 Synthesis of methyl3-[4-benzyloxy-5-bromo-3-(N-methylamino)phenyl]propionate (Compound No.B-105)

A solution of Compound No. B-100 (105 mg) in DMF (3 ml) was added with60% sodium hydride (20 mg) under ice cooling, and stirred for 10minutes. This reaction mixture was added dropwise with methyl iodide (32μl), stirred for 10 minutes, then warmed to room temperature, andfurther stirred for 2 hours. The reaction mixture was poured into water,and added with ethyl acetate (30 ml) for extraction. The organic layerwas successively washed with saturated aqueous sodium hydrogencarbonate,saturated aqueous ammonium chloride, and saturated brine and dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by column chromatography (Quad, hexane:ethyl acetate=6:1) toobtain the title compound (Compound No. B-105, 17 mg).

Example B-109 Synthesis of3-[4-benzyloxy-5-bromo-3-(N,N-dimethylamino)phenyl]propionic acid(Compound No. B-109)

A solution of Compound No. B-100 (105 mg) in DMF (3 ml) was added with60% sodium hydride (40 mg) under ice cooling, and stirred for 10minutes. This reaction mixture was added dropwise with methyl iodide(300 μl), stirred for 10 minutes, then warmed to room temperature, andfurther stirred for 16 hours. The reaction mixture was poured intowater, and added with ethyl acetate (30 ml) for extraction. The organiclayer was successively washed with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride, and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:ethyl acetate=6:1) to obtain the title compound (Compound No.B-109, 88 mg).

Examples B-113 and B-114 Syntheses of3-(3-bromo-4-cyclopentyloxy-5-hydroxyphenyl)propionic acid (Compound No.B-113) and 3-(5-acetoxy-3-bromo-4-cyclopentyloxyphenyl)propionic acid(Compound No. B-114)

A solution of Compound No. B-99 (415 mg) in acetic acid (1.5 ml) wasadded with 20% sulfuric acid (1.0 ml). This reaction mixture was addeddropwise with an aqueous solution (0.5 ml) of sodium nitrite (78 mg)over 10 minutes, while the temperature of the reaction mixture wasmaintained below 10° C., and further stirred for 5 minutes. Thisreaction mixture was added dropwise to a solution of sodium acetate (348mg) in acetic acid (3.5 ml) heated and stirred at 100° C. beforehandover 5 minutes, and further stirred for 10 minutes with heating. Thereaction solution was poured into ice water (50 ml), and extracted withisopropyl ether (100 ml×2). The organic layer was successively washedwith saturated aqueous sodium hydrogencarbonate, saturated aqueousammonium chloride and saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was purified bycolumn chromatography (Quad, hexane:ethyl acetate=10:1) to obtain thetitle compounds (Compound No. B-113, 47 mg and Compound No. B-114, 105mg).

Example B-117 Synthesis of methyl3-(3,5-dibromo-4-cyclopentylmethyloxyphenyl)propionate (Compound No.B-117)

A solution of Intermediate 1 (670 mg) in acetonitrile (30 ml) was addedwith NBS (990 mg), stirred at room temperature for 2 hours, then warmedto 40° C., and stirred for 18 hours. The reaction mixture wasconcentrated under reduced pressure, then added with ethyl acetate (100ml), and washed successively with saturated aqueous ammonium chloride,5% aqueous sodium sulfite, saturated aqueous sodium hydrogencarbonateand saturated brine. The organic layer was dried, and then the solventwas evaporated under reduced pressure. According to the proceduredescribed in the synthesis method of Compound No. A-6 with themodifications that the reaction was carried out for 18 hours under icecooling, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=10:1), the residue was reacted with Ph₃P(1460 mg), cyclopentane methanol (560 mg) and 40% DIAD (2.6 ml) andtreated to obtain the title compound (Compound No. B-117, 710 mg).

Examples A-1 to A-33

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-A-1. The compounds wereprepared according to the preparation methods of the compound numbers(e.g., “A-1”) or the intermediate numbers (e.g., “Int 2”) shown in thecolumns of “Syn” in the tables. “Int” means an intermediate compoundnumber. When the preparation required a plurality of steps, a pluralityof compound numbers or intermediate compound numbers are mentioned inthe columns of “Syn”. For example, an indication of “Int 2, A-1” in acolumn of “Syn” means that “the compound is prepared from a compoundprepared according to the procedure described in the synthesis method ofIntermediate 2 according to the procedure described in the synthesismethod of Compound No. A-1.” When the compounds were synthesizedaccording to the procedure described in the synthesis method of CompoundNo. A-6, TMAD or di-t-butyl azodicarboxylate (hereinafter abbreviated as“DBAB”) was sometimes used instead of 40% DIAD.

TABLE A-1

LCMS Exp. Rx′O Y′ Zx′ G Syn method RTime Mass A-1 cPenMeO Me H Br A-1 C341 (M⁺ + 1) A-2 cHexMeO Me H Br A-2 C 354 (M⁺) A-3 iBuO Me H Br A-2 A5.34 N.D A-4 2EtBuO Me H Br A-2 A-5 cPenO Me H Br A-5 C 326 (M⁺ ) A-6cHexO Me H Br A-6 C 340 (M⁺ ) A-7 cHepO Me H Br A-6 A-8 BnO Me H Br A-2A-9 1PhEtO Me H Br A-2 A-10 2FBnO Me H Br A-2 A-11 4FBnO Me H Br A-2A-12 2ClBnO Me H Br A-2 A-13 4ClBnO Me H Br A-2 A 4.85 N.D A-14 4MeBnOMe H Br A-2 A-15 4CF3BnO Me H Br A-2 A-16 2(4DMAPh)EtO Me H Br A-6 A-172(PhO)EtO Me H Br A-6 A 5.04 N.D A-18 1(2FPh)EtO Me H Br A-6 A-191(4ClPh)EtO Me H Br A-6 A 4.82 N.D A-20 cPenMeO Me Cl Br A-20 C 375(M⁺ + 1) A-21 cPenMeO Me F Br A-21 A-22 cPenO Me F Br A-21 C 345(M⁺ + 1) A-23 cHexO Me F Br A-21 A-24 cPenO Et Me Br A-24 A 5.82 N.DA-25 cPenO Et OMe Br A-25 A-26 cPenMeO Me NO2 Br A-26 C 340 (M⁺ + 1)A-27 cHexMeO Me NO2 Br A-26 A-28 cPenO Me NO2 Br A-26 C 372 (M⁺ + 1)A-29 cHexO Me NO2 Br A-26 A-30 2-IndanO Me NO2 Br A-26 A 5.03 N.D A-31PhO Me H Br A-31 A 5.15 N.D A-32 4ClPhO Me H Br A-31 A 5.47 N.D A-334MeOPhO Me H Br A-31 A 5.02 N.D

Examples B-1 to B-119

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-B-1 to Table B-3.

TABLE B-1

LCMS Exp. Rx′O Y′ Zx′ G Syn method RTime Mass B-1 nPrO Me H Br A-2 C 279(M⁺) B-2 iPrO Me H Br A-2 B-3 sBuO Me H Br A-6 B-4 iPenO Me H Br A-6 B-51,3DMeBuO Me H Br A-6 B-6 2MeBuO Me H Br A-6 B-7

Me H Br A-6 B-8

Me H Br A-6 B-9 2,3DMeBuO Me H Br A-6 B-10 cPenO Me H Cl A-6 C 361(M⁺ + 1) B-11 trans2Me,cPenO Me H Br A-6 B-12 3Me,cPenO Me H Br A-6 B-13trans2Me,cHexO Me H Br A-6 B-14 cis2Me,cHexO Me H Br A-6 B-15 3Me,cHexOMe H Br A-6 C 354 (M⁺ + 1) B-16 4Me,cHexO Me H Br A-6 B-17 2,3DMe,cHexOMe H Br A-6 B-18 3,4DMe,cHexO Me H Br A-6 C 368 (M⁺ + 1) B-193,5DMe,cHexO Me H Br A-6 B-20

Me H Br A-6 B-21

Me H Br A-6 B-22

Me H Br A-6 B-23 1PhPrO Me H Br A-6 B-24 (S)1PhPrO Me H Br A-6 B-25BenzhydrylO Me H Br A-6 B-26

Me H Br A-6 C 391 (M⁺ + 1) B-27

Me H Br A-6 B-28 2Ph,1MeEtO Me H Br A-6 B-29 2Ph,2MeEtO Me H Br A-6 B-302(2FPh),1MeEtO Me H Br A-6 B-31 2(3CF₃Ph),1MeEtO Me H Br A-6 B-32 3PhBuOMe H Br A-6 B-33 5OMe-2-IndanO Me H Br A-6 B-34 5,6D(OMe)-2-IndanO Me HBr A-6 B-35 5F-2-IndaneO Me H Br A-6 B-36 1-IndaneO Me H Br A-6 B-37

Me H Br A-6

TABLE B-2 B-38

Me H Br A-6 B-39 3FBnO Me H Br A-6 B-40 2MeBnO Me H Br A-6 C 363(M⁺ + 1) B-41 3MeBnO Me H Br A-6 B-42 3,5DMeBnO Me H Br A-6 B-43 4tBuBnOMe H Br A-6 B-44 2CF₃BnO Me H Br A-6 B-45 4CF₃BnO Me H Br A-6 B-463(CF₃O)BnO Me H Br A-6 B-47 4(CF₃O)BnO Me H Br A-6 B-48 4(nBuO)BnO Me HBr A-6 B-49

Me H Br A-6 C 406 (M⁺ + 1) B-50 3,4DFBnO Me H Br A-6 B-51 2,4DFBnO Me HBr A-6 B-52 4Br,2FBnO Me H Br A-6 B-53 2,4DClBnQ Me H Br A-6 B-543,4DClBnO Me H Br A-6 B-55 2,3DClBnO Me H Br A-6 B-56 2,6DClBnO Me H BrA-6 B-57 3,5DClBnO Me H Br A-6 B-58 2-NapMeO Me H Br A-6 C 399 (M⁺ + 1)B-59 1-NapMeO Me H Br A-6 B-60

Me H Br A-6 B-61

Me H Br A-6 B-62

Me H Br A-6 C 339 (M⁺ + 1) B-63 2PhBnO Me H Br A-6 B-64 4PhBnO Me H BrA-6 B-65 2PhEtO Me H Br A-6 B-66 2(2MePh)EtO Me H Br A-6 B-672(3MePh)EtO Me H Br A-6 B-68 2(4MePh)EtO Me H Br A-6 B-69 2(3FPh)EtO MeH Br A-6 B-70 2(3ClPh)EtO Me H Br A-6 B-71 2(2CF₃Ph)EtO Me H Br A-6 B-722(4CF₃Ph)EtO Me H Br A-6 B-73 2(2OMePh)EtO Me H Br A-6 B-74 2(2-Nap)EtOMe H Br A-6 C 413 (M⁺ + 1) B-75 2(3-Ind)EtO Me H Br A-6 B-76

Me H Br A-6 B-77 2(PhO)EtO Me H Br A-6 B-78 2(2ClPhO)EtO Me H Br A-6B-79 2(4ClPhO)EtO Me H Br A-6

TABLE B-3 B-80

Me H Br A-6 C 407 (M⁺ + 1) B-81

Me H Br A-6 B-82

Me H Br A-6 B-83

Me H Br A-6 B-84 2(PhS)EtO Me H Br A-6 C 379 (M⁺ + 1) B-85 2-BztO Me HBr A-6 B-86 (6OMe-2-Bzt)O Me H Br A-6 B-87 cPenO Me Cl Br A-20 B-881(4FPh)EtO Me Cl Br A-20 B-89 1PhEtO Me F Br A-21 B-90 1(4FPh)EtO Me FBr A-21 B-91 1PhEtO Et Me Br A-24 B-92 1(4FPh)EtO Et Me Br A-24 B-931PhEtO Me OMe Br A-25 B-94 1(4FPh)EtO Me OMe Br A-25 B-95 BnO Me NO2 BrA-26 B-96 2-IndanO Me NO2 Br A-26 A 4.44 N.D B-97 5OMe-2-IndanO Me NO2Br A-26 B-98 4CF3BnO Me NO2 Br A-26 B-99 cPenO Me NH2 Br B-99 C 342(M⁺ + 1) B-100 BnO Me NH2 Br B-99 B-101 1PhEtO Me NH2 Br B-99 B-1025OMe-2-IndanO Me NH2 Br B-99 B-103 BnO Me NHTFA Br B-103 B-104 cPenO MeNHTFA Br B-103 C 438 (M⁺ + 1) B-105 BnO Me NHMe Br B-105 B-106 cPenO MeNHMe Br B-105 C 356 (M⁺ + 1) B-107 1PhEtO Me NHMe Br B-105 B-1081(4FPh)EtO Me NHMe Br B-105 B-109 BnO Me NMe2 Br B-109 B-110 cPenO MeNMe2 Br B-109 C 370 (M⁺ + 1) B-111 1PhEtO Me NMe2 Br B-109 B-1121(4FPh)EtO Me NMe2 Br B-109 B-113 cPenO Me OH Br B-113 C 343 (M⁺ + 1)B-114 cPenO Me OCOMe Br B-114 B-115 1(4FPh)EtO Me OH Br B-113 B-1161(4FPh)EtO Me OCOMe Br B-114 B-117 cPenMeO Me Br Br B-117 B-118 cPenO MeBr Br B-117 A 5.98 N.D B-119 1(4FPh)EtO Me Br Br B-117

Example C-1 Synthesis of 3-bromo-4-cyclohexylmethyloxybenzaldehyde(Intermediate 25)

According to the procedure described in the synthesis method of CompoundNo. A-2 provided that the purification was performed by flash columnchromatography (hexane:isopropyl ether=5:1),3-bromo-4-hydroxybenzaldehyde (17.4 g), potassium carbonate (23.9 g) andbromomethylcyclohexane (36.2 ml) were reacted and treated to obtain thetitle compound (Intermediate 25, 18.7 g).

Synthesis of 4-cyclohexylmethyloxy-3-(naphthalen-2-yl)benzaldehyde(Compound No. C-1)

A solution of 2-naphthaleneboronic acid (535 mg) in methanol (5.0 ml),Intermediate 25 (1.16 g), and 2 M aqueous sodium carbonate (0.9 ml) wereadded with toluene (10.0 ml) and tetrakistriphenylphosphinepalladium(0)[hereinafter abbreviated as “(Ph₃P)₄Pd”] (116 mg, Nakarai Tecs), andstirred at 80° C. for 17 hours. The reaction mixture was added withethyl acetate (100 ml), and washed successively with saturated aqueoussodium hydrogencarbonate, saturated aqueous ammonium chloride andsaturated brine. The organic layer was dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:ethyl acetate=10:1) to obtain the titlecompound (Compound No. C-1, 345 mg).

Example D-10 Synthesis of 3-bromo-4-hydroxy-5-nitrobenzaldehyde(Intermediate 26)

A solution of 3-bromo-4-hydroxybenzaldehyde (6.30 g) in acetic acid (45ml) was added dropwise with 70% nitric acid (5.85 ml) on a water bath,then added with sodium nitrite (62 mg), and further stirred for 2 hours.The reaction mixture was poured into ice water (300 ml), andprecipitates were taken by filtration, and washed with water (50 ml×3).The precipitates were dried under reduced pressure for 24 hours toobtain the title compound (Intermediate 26, 5.88 g).

Synthesis of 3-bromo-4-cyclohexylmethyloxy-5-nitrobenzaldehyde(Intermediate 27)

According to the procedure described in the synthesis method of CompoundNo. A-2 provided that the purification was performed by flash columnchromatography (hexane:ethyl acetate=7:1), Intermediate 26 (5.5 g),potassium carbonate (3.94 g) and bromomethylcyclohexane (3.94 ml) werereacted and treated to obtain the title compound (Intermediate 27, 5.2g).

Synthesis of4-cyclohexylmethyloxy-3-(naphthalen-2-yl)-5-nitrobenzaldehyde (CompoundNo. D-10)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 15hours at 80° C., and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=7:1), Intermediate 27 (2.65g), 2-naphthaleneboronic acid (3.01 g), 2 M aqueous sodium carbonate(7.5 ml) and (Ph₃P)₄Pd (960 mg) were reacted and treated to obtain thetitle compound (Compound No. D-10, 2.96 g).

Examples C-1 to C-8

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-C-1.

TABLE C-1

Rx′O Zx′ AR′ LCMS Exp. Rx′O Position Zx′ Position AR′ Position Synmethod RTime Mass C-1 cHexMeO 4 H — 2-Nap 5 C-1 C-2 cHexMeO 4 H — 1-Nap5 C-1 C-3 cHexMeO 4 H — 2OMe-6-Nap 5 C-1 C 374(M⁺) C-4 cHexMeO 4 H —5-Ind 5 C-1 C-5 cPenMeO 4 H — 2-Nap 5 C-1 C-6 cPenMeO 4 H — 5-Ind 5 C-1C-7 cPenO 4 H — 2-Nap 5 C-1 C 316(M⁺) C-8 cPenO 4 H — 5-Ind 5 C-1 C305(M⁺)

Examples D-1 to D-29

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-D-1

TABLE D-1

Rx′O Zx′ AR′ LCMS Exp. Rx′O Position Zx′ Position AR′ Position Synmethod RTime Mass D-1 cHexMeO 4 H — 2-BT 3 C-1 C 350 (M⁺) D-2 cHexMeO 4H — 2-BF 3 C-1 D-3 cHexMeO 4 H — 1Me-5-Ind 3 C-1 C 316 (M⁺) D-4 cHexMeO4 H — 5-1HIdz 3 C-1 D-5 cHexMeO 4 H — 1Me-5-1HIdz 3 C-1 D-6 2(2FPh)EtO 4H — 2-Nap 3 C-1 D-7 2(2FPh)EtO 4 H — 5-Ind 3 C-1 D-8 2-IndanO 4 H —5-Ind 3 C-1 D-9 2-IndanO 4 H — 5-1HIdz 3 C-1 D-10 cPenMeO 4 NO2 5 2-Nap3 D-10 C 330 (M⁺ + 1) D-11 cPenMeO 4 NO2 5 5-Ind 3 D-10 D-12 cHexMeO 4NO2 5 2-Nap 3 D-10 D-13 cHexMeO 4 NO2 5 2-BF 3 D-10 D-14 cPenO 4 NO2 52-Nap 3 D-10 D-15 cPenO 4 NO2 5 5-Ind 3 D-10 C 350 (M⁺) D-16 2(2FPh)EtO4 NO2 5 2-Nap 3 D-10 D-17 2(2FPh)EtO 4 NO2 5 5-Ind 3 D-10 D-18 2-IndanO4 NO2 5 5-Ind 3 D-10 D-19 2-IndanO 4 NO2 5 1Me-5-1HIdz 3 D-10 A 3.85 414(M⁺ + 1) D-20 cPenO 2 H — 2-Nap 5 C-1 C 316 (M⁺) D-21 cPenO 2 H — 5-Ind5 C-1 C 305 (M⁺) D-22 cPenO 3 H — 2-Nap 5 C-1 D-23 cPenO 3 H — 5-Ind 5C-1 D-24 cPenO S H — 2-Nap 2 C-1 D-25 cPenO 5 H — 5-Ind 2 C-1 D-26 cPenO4 H — 2-Nap 2 C-1 D-27 cPenO 4 H — 5-Ind 2 C-1 D-28 cPenO 3 H — 2-Nap 2C-1 D-29 cPenO 3 H — 5-Ind 2 C-1

Example E-1 Synthesis of 5-bromo-2-cyclopentylmethyloxypyridine(Intermediate 28)

A solution of potassium t butoxide (550.6 mg, WAKO) in dehydrated THF(10 ml) was added with cyclopentane methanol (450 μl), and then addedwith a solution of 2,5-dibromopyridine (982.8 mg, TCI) in dehydrated THF(15 ml) under ice cooling. The reaction mixture was stirred for 30minutes, then warmed to room temperature, and stirred for 11 hours. Thereaction mixture was added with water (100 ml) and ethyl acetate (60 ml)for extraction. The organic layer was washed successively with saturatedaqueous sodium hydrogencarbonate and saturated brine sequentially, anddried, and then the solvent was evaporated under reduced pressure. Theresidue was purified by column chromatography (Quad, hexane:ethylacetate=15:1) to obtain the title compound (Intermediate 28, 896 mg).

Synthesis of 2-cyclopentylmethyloxypyridine-5-carbaldehyde (Intermediate29)

A solution of Intermediate 28 (895 mg) in anhydrous THF (10 ml) wasadded dropwise with a 1.6 M solution of n-butyllithium in hexane (2.70ml, Ald) over 5 minutes with cooling at −78° C. under argon gasatmosphere, and stirred for 20 minutes. This reaction mixture was addedwith dehydrated DMF (330 μl, WAKO) over 3 minutes, stirred for 30minutes, then warmed to room temperature, and further stirred for 1hour. The reaction mixture was added with water (10 ml), and extractedwith ethyl acetate (30 ml×3). The organic layer was washed withsaturated brine and dried, and then the solvent was evaporated underreduced pressure. The residue was purified by column chromatography(Quad, hexane:ethyl acetate=10:1) to obtain the title compound(Intermediate 29, 1.04 g).

Synthesis of ethyl 3-(2-cyclopentylmethyloxypyridin-5-yl)acrylate(Intermediate 30)

According to the procedure described in the synthesis method ofIntermediate 7 with the modification that the reaction was carried outfor 1 hour, Intermediate 29 (450 mg), ethyl diethylphosphonoacetate(530/1) and 60% sodium hydride (120 mg) were reacted and treated toobtain the title compound (Intermediate 30, 394 mg).

Synthesis of ethyl 3-(2-cyclopentylmethyloxypyridine-5-yl)propionate(Intermediate 31)

According to the procedure described in the synthesis method ofIntermediate 8 with the modifications that the reaction was carried outfor 1 hour, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=15:1), Intermediate 30 (392 mg) and 10%palladium/carbon (30 mg) were reacted and treated to obtain the titlecompound (Intermediate 31, 246 mg).

Synthesis of ethyl3-(3-bromo-2-cyclopentylmethyloxypyridin-5-yl)propionate (Compound No.E-1)

A solution of Intermediate 31 (5.20 g) in acetonitrile (50 ml) waswarmed to 35° C., added dropwise with bromine (1.1 ml, WAKO), then addedwith NBS (3.72 g), and stirred at room temperature for 2 hours. Thereaction mixture was concentrated under reduced pressure, then addedwith ethyl acetate (200 ml), and washed successively with saturatedaqueous ammonium chloride, 5% aqueous sodium sulfite, saturated aqueoussodium hydrogencarbonate and saturated brine. The organic layer wasdried, and then the solvent was evaporated under reduced pressure. Theresidue was purified by column chromatography (Quad, hexane:ethylacetate=10:1) to obtain the title compound (Compound No. E-1, 6.51 g).

Example E-7 Synthesis of 2-benzyloxy-5-bromopyridine (Intermediate 32)

According to the procedure described in the synthesis method ofIntermediate 28 provided that the reaction was carried out for 1 hour,potassium t-butoxide (3.13 g), benzyl alcohol (3.10 ml) and2,5-dibromopyridine (4.79 g) were reacted and treated to obtain thetitle compound (Intermediate 32, 5.36 g).

Synthesis of 2-benzyloxypyridine-5-carbaldehyde (Intermediate 33)

According to the procedure described in the synthesis method ofIntermediate 29, Intermediate 32 (5.10 g), a 1.6M solution ofn-butyllithium in hexane (15.5 ml) and dehydrated DMF (1.9 ml) werereacted and treated to obtain the title compound (Intermediate 33, 2.75g).

Synthesis of ethyl 3-(2-benzyloxypyridin-5-yl)acrylate (Intermediate 34)

According to the procedure described in the synthesis method ofIntermediate 7, Intermediate 33 (2.74 g), ethyl diethylphosphonoacetate(3.12 ml) and 60% sodium hydride (635 mg) were reacted and treated toobtain the title compound (Intermediate 34, 2.12 g).

Synthesis of ethyl 3-(2-hydroxypyridin-5-yl)propionate (Intermediate 35)

According to the procedure described in the synthesis method ofIntermediate 8 provided that the reaction was carried out for 2.5 hours,Intermediate 54 (2.12 g) and 10% palladium/carbon (120 mg) were reactedand treated to obtain the title compound (Intermediate 35, 1.26 g).

Synthesis of ethyl 3-(3-bromo-2-hydroxypyridin-5-yl)propionate(Intermediate 36)

According to the procedure described in the synthesis method of CompoundNo. E-1 with the modifications that the reaction was carried out for 2.5hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=1:2), Intermediate 35 (1.23 g), bromine (340μl) and NBS (1.19 g) were reacted and treated to obtain the titlecompound (Compound No. 36, 1.42 g).

Synthesis of ethyl3-[5-bromo-6-[(S)-1-phenylethyloxy]pyridin-3-yl]propionate (Compound No.E-7)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for 11hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=4:1), Intermediate 36 (137 mg), Ph₃P (273mg), (R)-1-phenylethanol (150 μl, TCI) and 40% DIAD (400 μl) werereacted and treated to obtain the title compound (Compound No. E-7, 167mg).

Example E-13 Synthesis of ethyl3-(5-bromo-6-(4-trifluoromethylbenzyloxy)pyridin-3-yl)propionate(Compound No. E-13)

A solution of Intermediate 36 (71.5 mg) in chloroform (7 ml) was addedwith 4-trifluoromethylbenzyl bromide (109.2 mg, TCI) and silvercarbonate (120 mg, WAKO), and stirred at room temperature for 11 hoursunder light shielding. The reaction mixture was filtered, and thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=6:1) to obtain thetitle compound (Compound No. E-13, 114 mg).

Example E-1 to 16

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-E-1.

TABLE E-1

LCMS Exp. Rx′O Y′ G Syn method RTime Mass E-1 cPenMeO Et Br E-1 A 5.98356 (M⁺) E-2 cHexMeO Et Br E-1 E-3 iBuO Et Br E-1 A 5.57 N.D E-4 2EtBuOEt Br E-1 E-5 cPenO Et Br E-1 A 5.62 342 (M⁺) E-6 cHexO Et Br E-1 E-7(R)1PhEtO Et Br E-7 A 5.60 N.D E-8 2(4DMAPh)EtO Et Br E-7 E-9 2(2FPh)EtOEt Br E-7 E-10 2(3FPh)EtO Et Br E-7 E-11 2(4ClPh)EtO Et Br E-7 E-122(PhO)EtO Et Br E-7 E-13 4CF₃BnO Et Br E-13 A 5.78 432 (M⁺) E-14 2MeBnOEt Br E-13 E-15 2ClBnO Et Br E-13 E-16 1(4FPh)EtO Et Br E-7

Example F-1 Synthesis of 4-(3-bromo-4-methoxyphenyl)butyric acid(Intermediate 37)

According to the procedure described in the synthesis method of CompoundNo. A-1 provided that the reaction was carried out under ice cooling for30 minutes and for 20 hours at room temperature,4-(4-methoxyphenyl)butyric acid (11.64 g, Ald) and NBS (11.21 g) werereacted and treated to obtain the title compound (Intermediate 37, 16.30g).

Synthesis of methyl 4-(3-bromo-4-hydroxyphenyl)butyrate (Intermediate38)

According to the procedure described in the synthesis method ofIntermediate 4, Intermediate 37 (12.51 g) and a 1 M solution of borontribromide in methylene chloride (100 ml) were reacted and treated, andthe obtained residue was reacted with thionyl chloride (8.4 ml) inmethanol and treated according to the procedure described in thesynthesis method of Intermediate 1 to obtain the title compound(Intermediate 38, 10.48 g).

Synthesis of methyl 4-(3-bromo-4-cyclopentylmethyloxyphenyl)butyrate(Compound No. F-1)

According to the procedure described in the synthesis method of CompoundNo. A-6 provided that the purification was performed by columnchromatography (Quad, hexane:isopropyl alcohol=10:1), Intermediate 38(2.72 g), Ph₃P (7.86 g), cyclopentane methanol (3.24 ml) and 40% DIAD(14.2 ml) were reacted and treated to obtain the title compound(Compound No. F-1, 3.33 g).

Examples F-1 to F-4

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-F-1.

TABLE F-1

LCMS Exp. Rx′O Y′ Zx′ G n Syn method RTime Mass F-1 cPenMeO Me H Br 3F-1 C 354(M⁺) F-2 cPenO Me H Br 3 F-1 F-3 cHexO Me H Br 3 F-1 C 354(M⁺)F-4 1(4FPh)EtO Me H Br 3 F-1

Example G-1 Synthesis of methyl3-[4-methoxy-3-(naphthalen-2-yl)phenyl]propionate (Intermediate 39)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 2hours, and the purification was performed by flash column chromatography(hexane:isopropyl ether=8:1), Intermediate 20 (460 mg),2-naphthaleneboronic acid (886 mg), 2 M aqueous sodium carbonate (1.6ml) and (Ph₃P)₄Pd (298 mg) were reacted and treated to obtain the titlecompound (Intermediate 39, 580 mg).

Synthesis of 3-[4-methoxy-3-(naphthalen-2-yl)phenyl]propionic acid(Intermediate 40)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Intermediate 39 (773 mg) and 2 N aqueous sodium hydroxide (2.3 ml) werereacted and treated to obtain the title compound (Intermediate 40, 674mg).

Synthesis of methyl 3-[4-hydroxy-3-(naphthalen-2-yl)phenyl]propionate(Intermediate 41)

According to the procedure described in the synthesis method ofIntermediate 10, pyridine (5 ml), concentrated hydrochloric acid (5 ml),and Intermediate 40 (551 mg) were reacted and treated to obtain crudepowder substance. This substance was reacted with thionyl chloride (282μl) in methanol and treated according to the procedure described in thesynthesis method of Intermediate 1 to obtain the title compound(Intermediate 41, 531 mg).

Synthesis of methyl3-[4-cyclopentyloxy-3-(naphthalen-2-yl)phenyl]propionate (Compound No.G-1).

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for 15hours, and the purification was performed by flash column chromatography(hexane:isopropyl ether=6:1), Intermediate 41 (100 mg), Ph₃P (262 mg),cyclopentanol (91 μl, TCI) and 40% DIAD (473 μl) were reacted andtreated to obtain the title compound (Compound No. G-1, 120 mg).

Example G-2 Synthesis of3-[4-cyclopentyloxy-3-(naphthalen-2-yl)phenyl]propionic acid (CompoundNo. G-2)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 4 hours,Compound No. G-1 (115 mg), and 2 N aqueous sodium hydroxide (0.75 ml)were reacted and treated to obtain the title compound (Compound No. G-2,108 mg).

Example G-3 Synthesis of methyl3-[4-cyclopentyloxy-3-(1H-indol-5-yl)phenyl]propionate (Compound No.G-3)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 3hours, and the purification was performed by flash column chromatography(hexane:ethyl acetate=4:1), Compound No. A-6 (833 mg), 5-indoleboronicacid (657 mg), 2 M aqueous sodium carbonate (2.4 ml) and (Ph₃P)₄Pd (233mg) were reacted and treated to obtain the title compound (Compound No.G-3, 900 mg).

Example G-4 Synthesis of3-[4-cyclopentyloxy-3-(1H-indole-5-yl)phenyl]propionic acid (CompoundNo. G-4)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. G-3 (144 mg) and 2 N aqueous sodium hydroxide (420 μl) werereacted and treated to obtain the title compound (Compound No. G-4, 127mg).

Example G-9 Synthesis of methyl3-[4-benzyloxy-5-(1-methyl-1H-indazol-5-yl)phenyl]propionate (CompoundNo. G-9)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 6 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=4:1), Compound No. A-8 (349mg), 1-methyl-1H-indazole-5-boronic acid (283 mg), 2 M aqueous sodiumcarbonate (0.9 ml) and (Ph₃P)₄Pd (94.3 mg) were reacted and treated toobtain the title compound (Compound No. G-9, 370 mg).

Example G-10 Synthesis of3-[4-benzyloxy-5-(1-methyl-1H-indazol-5-yl)phenyl]propionic acid(Compound No. G-10)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 4 hours,Compound No. G-9 (80 mg) and 2 N aqueous sodium hydroxide (0.20 ml) werereacted and treated to obtain the title compound (Compound No. G-10, 71mg).

Synthesis of methyl3-[4-hydroxy-5-(1-methyl-1H-indazol-5-yl)phenyl]propionate (Intermediate42)

A solution of Compound No. G-9 (314 mg) in a mixture of ethyl acetate (3ml) and methanol (3 ml) was added with 10% palladium/carbon (12 mg), andstirred at room temperature for 16 hours under hydrogen atmosphere. Thereaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure to obtain the title compound(Intermediate 48, 288 mg).

Example G-23 Synthesis of methyl3-(3-bromo-4-t-butyldimethylsilyloxyphenyl)propionate (Intermediate 43)

According to the procedure described in the synthesis method ofIntermediate 16 provided that the reaction was carried out for 16 hours,Intermediate 5 (5.18 g), imidazole (2.04 g) and t-butyldimethylsilylchloride (4.52 g) were reacted and treated to obtain the title compound(Intermediate 43, 8.42 g).

Synthesis of methyl3-[4-(t-butyldimethylsilyloxy-3-(1H-indol-5-yl)phenyl)propionate(Intermediate 44)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that reaction was performed for 12.5hours, and the purification was performed by flash column chromatography(hexane:ethyl acetate=9:1), 5-indoleboronic acid (4.83 g), Intermediate34 (7.46 g), 2 M aqueous sodium carbonate (18 ml) and (Ph₃P)₄Pd (1.62 g)were reacted and treated to obtain the title compound (Intermediate 44,5.04 g).

Synthesis of methyl 3-[4-hydroxy-3-(1H-indol-5-yl)phenyl]propionate(Intermediate 45)

According to the procedure described in the synthesis method ofIntermediate 19 with the modifications that the reaction was carried outfor 2 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=3:1), Intermediate 35 (5.04 g), acetic acid(2.8 ml) and a 1 M solution of tetrabutylammonium fluoride in THF (49ml, TCI) were reacted and treated to obtain the title compound(Intermediate 45, 3.13 g).

Synthesis of methyl3-[3-(1H-indol-5-yl)-4-(4-methylphenylmethyloxy)phenyl]-propionate(Compound No. G-23)

According to the procedure described in the synthesis method of CompoundNo. A-2 with the modifications that the reaction was carried out for 15hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), Intermediate 45 (80 mg), potassiumcarbonate (114 mg) and 4-methylbenzyl bromide (54 μl, TCI) were reactedand treated to obtain the title compound (Compound No. G-23, 104 mg).

Example G-24 Synthesis of3-[3-(1H-indol-5-yl)-4-(4-methylphenylmethyloxy)phenyl]propionic acid(Compound No. G-24)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. G-23 (99 mg) and 2 N aqueous sodium hydroxide (500 μl) werereacted and treated to obtain the title compound (Compound No. G-24, 84mg).

Example G-106 Synthesis of N-[2-(t-butyldiphenylsilyloxy)ethyl]aniline(Intermediate 46)

A solution of 2-anilinoethanol (5.82 g, TCI) in anhydrous DMF (50 ml)was added with imidazole (3.23 g, TCI), added dropwise with a solutionof t-butyldiphenylsilyl chloride (12.48 g, TCI) in DMF (50 ml) under icecooling, stirred for 30 minutes, then warmed to room temperature, andfurther stirred for 3.5 hours. The reaction mixture was added with water(100 ml), and extracted with ethyl acetate (100 ml). The organic layerwas washed successively with water and saturated brine, and dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by flash column chromatography (hexane:ethyl acetate=9:1) toobtain the title compound (Intermediate 46, 15.61 g).

Synthesis of N-benzyl-N-[2-(t-butyldiphenylsilyloxy)ethyl]aniline(Intermediate 47)

According to the procedure described in the synthesis method of CompoundNo. A-2 with the modifications that the reaction was carried out for 15hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), Intermediate 46 (15.60 g), potassiumcarbonate (8.91 g) and benzyl bromide (6.05 ml, TCI) were reacted andtreated to obtain the title compound (Intermediate 47, 19.23 g).

Synthesis of 2-(N-benzyl-N-phenylamino)ethanol (Intermediate 48)

According to the procedure described in the synthesis method ofIntermediate 9 with the modifications that the reaction was carried outfor 1 hour, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=5:1), Intermediate 47 (19.22 g) anda 1 M solution of tetrabutylammonium fluoride in THF (86 ml) werereacted and treated to obtain the title compound (Intermediate 48, 9.06g).

Synthesis of methyl3-{4-[2-(N-benzyl-N-phenylamino)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionate(Compound No. G-106)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for 15hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=7:1), Intermediate 41 (1.26 g), Ph₃P (1.34g), Intermediate 48 (1.01 g) and DBAB (1.18 g) instead of 40% DIAD werereacted and treated to obtain the title compound (Compound No. G-106,1.39 g).

Example G-107 Synthesis of methyl3-{3-(naphthalen-2-yl)-4-[2-(N-phenylamino)ethyloxy]phenyl}propionate(Compound No. G-107)

A solution of Compound No. G-106 (1.39 g) in a mixture of THF (10 ml)and methanol (20 ml) was added with concentrated hydrochloric acid (75μl, WAKO) and 10% palladium/carbon (142 mg), and stirred at roomtemperature for 3 hours under hydrogen gas atmosphere. The reactionmixture was filtered, and the solvent of the filtrate was evaporatedunder reduced pressure to obtain the title compound (Compound No. G-107,842 mg).

Example G-108 Synthesis of3-{3-(naphthalen-2-yl)-4-[2-(phenylamino)ethyloxy]phenyl}propionic acid(Compound No. G-108)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. G-107 (46 mg) and 2 N aqueous sodium hydroxide (0.25 ml)were reacted and treated to obtain the title compound (Compound No.G-108, 41 mg).

Examples G-1 to G-121

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-G-1 to Table-G-4.

TABLE G-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass G-1 cPenMeO Me H 2-Nap G-1 C388 (M⁺) G-2 cPenMeO H H 2-Nap G-2 C 375 (M⁺ + 1) G-3 cPenMeO Me H 5-IndG-3 G-4 cPenMeO H H 5-Ind G-4 C 363 (M⁺) G-5 cPenMeO Me H 1Me-5-Ind G-3G-6 cPenMeO H H 1Me-5-Ind G-4 A 391 (M⁺ + 1) G-7 cPenMeO Me H 5-1HIdzG-3 G-8 cPenMeO H H 5-1HIdz G-4 G-9 BnO Me H 1Me-5-1HIdz G-9 G-10 BnO HH 1Me-5-1HIdz G-10 G-11 cPenMeO Me H 1Me-5-1HIdz G-3 G-12 cPenMeO H H1Me-5-1HIdz G-4 G-13 2EtBuO H H 2-Nap G-1,G-2 A 377 (M⁺ + 1) G-14 2EtBuOH H 5-Ind G-3,G-4 G-15 4Me,cHexO H H 2-Nap G-1,G-2 G-16 4Me,cHexO H H5-Ind G-3,G-4 D 5.46 378 (M⁺ + 1) G-17

H H 2-Nap G-1,G-2 G-18

H H 5-Ind G-3,G-4 G-19 cHepO H H 5-Ind G-3,G-4 G-20 3PhPrO H H 2-NapG-1,G-2 G-21 4PhBuO H H 5-Ind G-3,G-4 G-22

H H 2-Nap G-1,G-2 D 5.40 414 (M⁺ + 1) G-23 4MeBnO Me H 5-Ind G-23 G-244MeBnO H H 5-Ind G-24 G-25 2(4MePh)EtO H H 2-Nap G-1,G-2 G-262(4MePh)EtO H H 5-Ind G-1,G-2 G-27 4ClBnO H H 2-Nap G-23,G-24 G-284CF₃BnO H H 5-Ind G-23,G-24 G-29 3F,4(OMe)BnO H H 2-Nap G-1,G-2 G-303F,4(OMe)BnO H H 5-Ind G-1,G-2 G-31

H H 2-Nap G-1,G-2 G-32

H H 5-Ind G-1,G-2 G-33

H H 2-Nap G-1,G-2 G-34

H H 5-Ind G-1,G-2 G-35

H H 2-Nap G-1,G-2 G-36

H H 5-Ind G-1,G-2

TABLE G-2 G-37 1IndanO H H 5-Ind G-1,G-2 D 5.19 398 (M⁺ + 1) G-382IndanO H H 2-Nap G-1,G-2 G-39 2IndanO H H 5-Ind G-1,G-2 G-405OMe-2-IndanO H H 2-Nap G-1,G-2 C 439 (M⁺ + 1) G-41 5,6D(OMe)-2-IndanO HH 5-Ind G-1,G-2 C 458 (M⁺ + 1) G-42 5F-2-IndanO H H 2-Nap G-1,G-2 G-435F-2-IndanO H H 5-Ind G-1,G-2 C 416 (M⁺ + 1) G-44

H H 2-Nap G-1,G-2 G-45

H H 5-Ind G-1,G-2 A 5.46 412 (M⁺ + 1) G-46

H H 2-Nap G-1,G-2 G-47

H H 5-1HInd G-1,G-2 G-48 2(2MePh)EtO H H 2-Nap G-1,G-2 G-49 2(2MePh)EtOH H 5-Ind G-1,G-2 G-50 2(3FPh)EtO H H 2-Nap G-1,G-2 G-51 2(2ClPh)EtO H H2-Nap G-1,G-2 G-52 2(3ClPh)EtO H H 5-Ind G-1,G-2 G-53 2(2CF₃Ph)EtO H H5-Ind G-1,G-2 G-54 4(CF₃Ph)EtO H H 2-Nap G-1,G-2 G-55 2(2OMePh)EtO H H2-Nap G-1,G-2 C 427 (M⁺ + 1) G-56 2(4OMePh)EtO H H 5-Ind G-1,G-2 G-572(1-NapEt)O H H 2-Nap G-1,G-2 G-58 2(2-Nap)EtO H H 2-Nap G-1,G-2 G-592(2-Nap)EtO H H 5-Ind G-1,G-2 C 435 (M⁺) G-60 2(4ClPh)EtO H H 2-NapG-1,G-2 G-61

H H 5-Ind G-1,G-2 D 5.11 430 (M⁺ + 1) G-62

H H 1Me-5-1HIdz G-1,G-2 G-63 2(PhS)EtO H H 2-Nap G-1,G-2 A 402 (M⁺ + 1)G-64 2(PhS)EtO H H 5-Ind G-1,G-2 G-65 3PhPrO H H 5-Ind G-1,G-2 G-662ClBnO H H 2-Nap G-1,G-2 G-67 2BrBnO H H 5-Ind G-1,G-2 C 450 (M⁺) G-683,5DMeBnO H H 5-Ind G-1,G-2 G-69 4tBuBnO H H 2-Nap G-1,G-2 G-70 2CF₃BnOH H 2-Nap G-1,G-2 G-71 4CF₃BnO H H 5-Ind G-1,G-2 G-72 4nBuBnO H H 5-IndG-1,G-2 G-73 3,5DClBnO H H 2-Nap G-1,G-2 G-74 2,3DClBnO H H 5-IndG-1,G-2 G-75 2PhBnO H H 2-Nap G-1,G-2 G-76 4PhBnO H H 5-Ind G-1,G-2 A448 (M⁺ + 1)

TABLE G-3 G-77

H H 2-Nap G-1,G-2 G-78

H H 5-Ind G-1,G-2 G-79

H H 2-Nap G-1,G-2 G-80

H H 5-Ind G-1,G-2 G-81

H H 2-Nap G-1,G-2 C 386 (M⁺ + 1) G-82

H H 5-Ind G-1,G-2 G-83

H H 2-Nap G-1,G-2 G-84

H H 5-Ind G-1,G-2 G-85

H H 2-Nap G-1,G-2 G-86

H H 5-Ind G-1,G-2 G-87

H H 2-Nap G-1,G-2 G-88

H H 5-Ind G-1,G-2 G-89

H H 2-Nap G-1,G-2 G-90

H H 5-Ind G-1,G-2 G-91

H H 2-Nap G-1,G-2 G-92

H H 5-Ind G-1,G-2 G-93

H H 2-Nap G-1,G-2 G-94

H H 2-Nap G-1,G-2 C 384 (M⁺ + 1) G-95

H H 5-Ind G-1,G-2 G-96

H H 2-Nap G-1,G-2 G-97

H H 5-Ind G-1,G-2

TABLE-G-4 G-98

H H 2-Nap G-1, G-2 G-99

H H 5-Ind G-1, G-2 G-100

H H 2-Nap G-1, G-2 G-101

H H 5-Ind G-1, G-2 C 423(M⁺ + 1) G-102

H H 2-Nap G-1, G-2 G-103

H H 5-Ind G-1, G-2 G-104

H H 2-Nap G-1, G-2 G-105

H H 5-Ind G-1, G-2 G-106 2(Ph, BnN)EtO Me H 2-Nap G-106 G-107 2(PhNH)EtOMe H 2-Nap G-107 G-108 2(PhNH)EtO H H 2-Nap G-108 C 412(M⁺ + 1) G-1092(PhNH)EtO Me H 5-Ind G-107 G-110 2(PhNH)EtO H H 5-Ind G-108 G-1112(PhNH)EtO Me H 1Me-5-Ind G-107 G-112 2(PhNH)EtO H H 1Me-5-Ind G-108 C415(M⁺ + 1) G-113 2(PhNH)EtO Me H 5-1HIdz G-107 G-114 2(PhNH)EtO H H5-1HIdz G-108 G-115 2(PhNH)EtO Me H 1Me-5-1HIdz G-107 A 4.76 430(M⁺ + 1)G-116 2(PhNH)EtO H H 1Me-5-1HIdz G-108 C 416(M⁺ + 1) G-117 iBuO H H1Me-5-Ind G-1, G-2 C 352(M⁺ + 1) G-118 iBuO H H 1Me-5-1HIdz G-1, G-2 C353(M⁺ + 1) G-119 PhO H H 1Me-5-1HIdz G-3, G-4 A 4.10 373(M⁺ + 1) G-1204ClPhO H H 1Me-5-1HIdz G-3, G-4 A 4.46 407(M⁺ + 1) G-121 4MeOPhO H H1Me-5-1HIdz G-3, G-4 A 4.12 403(M⁺ + 1)

Examples H-1 to H-32

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification are shown inTable-H-1 and Table-H-2.

TABLE-H-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass H-1

Me H 2-Nap G-1 H-2

H H 2-Nap G-2 H-3

Me H 5-Ind G-1 C 375 (M⁺ + 1) H-4

H H 5-Ind G-2 H-5

Me H 1Me-5-Ind G-1 H-6

H H 1Me-5-Ind G-2 H-7

Me H 5-1HIdz G-1 H-8

H H 5-1HIdz G-2 H-9

Me H 1Me-5-1HIdz G-1 H-10

H H 1Me-5-1HIdz G-2 C 454 (M⁺ + 1) H-11

H H 2-Nap G-1, G-2 H-12

H H 1Me-5-Ind G-1, G-2 C 452 (M⁺ + 1) H-13

H H 2-Nap G-1, G-2 H-14

H H 1Me-5-Ind G-1, G-2 H-15

H H 2-Nap G-1, G-2 C 464 (M⁺ + 1) H-16

H H 1Me-5-Ind G-1, G-2 H-17

H H 2-Nap G-1, G-2 C 450 (M⁺ + 1) H-18

H H 1Me-5-Ind G-1, G-2

TABLE-H-2 H-19

H H 2-Nap G-1, G-2 H-20

H H 1Me-5-Ind G-1, G-2 H-21

H H 2-Nap G-1, G-2 H-22

H H 1Me-5-Ind G-1, G-2 C 471 (M⁺ + 1) H-23

H H 2-Nap G-1, G-2 H-24

H H 1Me-5-Ind G-1, G-2 H-25

H H 2-Nap G-1, G-2 H-26

H H 1Me-5-Ind G-1, G-2 H-27

H H 2-Nap G-1, G-2 H-28

H H 1Me-5-Ind G-1, G-2 C 460 (M⁺ + 1) H-29

H H 2-Nap G-1, G-2 H-30

H H 1Me-5-Ind G-1, G-2 H-31

H H 2-Nap G-1, G-2 C 452 (M⁺ + 1) H-32

H H 1Me-5-Ind G-1, G-2

Example J-1 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-fluoro-5-(1H-indol-5-yl)phenyl]propionate(Compound No. J-1)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 13hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=10:1), Compound No. A-21 (154 mg),5-indoleboronic acid (100 mg), 2 M aqueous sodium carbonate (1.5 ml) and(Ph₃P)₄Pd (50 mg) were reacted and treated to obtain the title compound(Compound No. J-1, 125 mg).

Example J-2 Synthesis of3-[4-cyclopentylmethyloxy-3-fluoro-5-(1H-indol-5-yl)phenyl]propionicacid (Compound No. J-2)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. J-1 (124 mg) and 2 N aqueous sodium hydroxide (630 μl) werereacted and treated to obtain the title compound (Compound No. J-2, 97mg)

Example J-3 Synthesis of methyl3-[3-chloro-4-cyclopentylmethyloxy-5-(1H-indol-5-yl)phenyl]propionate(Compound No. J-3)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 13hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=10:1), Compound No. A-20 (151 mg),5-indoleboronic acid (97 mg), 2 M aqueous sodium carbonate (1.5 ml) and(Ph₃P)₄Pd (46 mg) were reacted and treated to obtain the title compound(Compound No. J-3, 160 mg).

Example J-4 Synthesis of3-[3-chloro-4-cyclopentylmethyloxy-5-(1H-indol-5-yl)phenyl]propionicacid (Compound No. J-4)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. J-3 (135 mg) and 2 N aqueous sodium hydroxide (660 μl) werereacted and treated to obtain the title compound (Compound No. J-4, 97mg).

Examples J-1 to J-92

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-J-1 to Table-J-3

TABLE-J-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass J-1 cPenMeO Me F 5-Ind J-1 A396 (M⁺ + 1) J-2 cPenMeO H F 5-Ind J-2 J-3 cPenMeO Me Cl 5-Ind J-3 J-4cPenMeO H Cl 5-Ind J-4 C 398 (M⁺ + 1) J-5 cPenMeO Me F 2-Nap J-1 J-6cPenMeO H F 2-Nap J-2 J-7 cPenMeO Me F 1Me-5-Ind J-1 J-8 cPenMeO H F1Me-5-Ind J-2 J-9 cPenMeO Me F 5-1HIdz J-1 J-10 cPenMeO H F 5-1HIdz J-2J-11 cPenMeO Me F 1Me-5-1HIdz J-1 J-12 cPenMeO H F 1Me-5-1HIdz J-2 C 397(M⁺ + 1) J-13 2EtBuO H F 2-Nap G-1, G-2 J-14 2EtBuO H F 5-Ind G-1, G-2J-15 4Me, cHexO H F 2-Nap G-1, G-2 J-16 4Me, cHexO H F 1Me-5-Ind G-1,G-2 J-17

H F 2-Nap G-1, G-2 J-18

H F 1Me-5-Ind G-1, G-2 C 452 (M⁺ + 1) J-19 cHepO H F 2-Nap G-1, G-2 J-203PhPrO H F 1Me-5-Ind G-1, G-2 J-21 4PhBuO H F 2-Nap G-1, G-2 J-22

H F 1Me-5-Ind G-1, G-2 J-23 1(4MePh)EtO H F 2-Nap G-1, G-2 J-24 4ClBnO HF 1Me-5-Ind G-1, G-2 J-25 4CF3BnO H F 2-Nap G-1, G-2 J-26 3F, 4(OMe)BnOH F 1Me-5-Ind G-1, G-2 J-27

H F 2-Nap G-1, G-2 C 429 (M⁺ + 1) J-28

H F 1Me-5-Ind G-1, G-2 J-29

H F 1Me-5-Ind G-1, G-2 J-30

H F 2-Nap G-1, G-2 J-31

H F 2-Nap G-1, G-2

TABLE-J-2 J-32 1-IndanO H F 2-Nap G-1, G-2 J-33 2-IndaneO H F 1Me-5-IndG-1, G-2 J-34 1-IndaneO H F 2-Nap G-1, G-2 J-35 5OMe-2-IndanO H F1Me-5-Ind G-1, G-2 J-36 5,6D(OMe)-2-IndanO H F 2-Nap G-1, G-2 J-375F-2-IndanO H F 2-Nap G-1, G-2 J-38 5F-2-IndanO H F 1Me-5-Ind G-1, G-2J-39

H F 2-Nap G-1, G-2 C 441 (M⁺ + 1) J-40

H F 1Me-5-Ind G-1, G-2 J-41 2(3MePh)EtO H F 2-Nap G-1, G-2 J-422(4MePh)EtO H F 1Me-5-Ind G-1, G-2 J-43 2(2ClPh)EtO H F 1Me-5-Ind G-1,G-2 J-44 2(3ClPh)EtO H F 2-Nap G-1, G-2 J-45 2(2CF₃Ph)EtO H F 2-Nap G-1,G-2 J-46 2(2OMePh)EtO H F 1Me-5-Ind G-1, G-2 J-47 2(4OMePh)EtO H F 2-NapG-1, G-2 J-48 2(2-Nap)EtO H F 1Me-5-Ind G-1, G-2 J-49

H F 2-Nap G-1, G-2 C 458 (M⁺ + 1) J-50

H F 1Me-5-IHIdz G-1, G-2 J-51 2(PhS)EtO H F 1Me-5-Ind G-1, G-2 J-523PhPrO H F 2-Nap G-1, G-2 J-53 2ClBnO H F 1Me-5-Ind G-1, G-2 J-54 2BrBnOH F 2-Nap G-1, G-2 J-55 3,5DMeBnO H F 2-Nap G-1, G-2 J-56 4tBuBnO H F1Me-5-Ind G-1, G-2 C 460 (M⁺ + 1) J-57 2CF₃BnO H F 1Me-5-Ind G-1, G-2J-58 4CF₃BnO H F 2-Nap G-1, G-2 J-59 4nBuOBnO H F 2-Nap G-1, G-2 J-603,5DClBnO H F 1Me-5-Ind G-1, G-2 J-61 2,3DClBnO H F 2-Nap G-1, G-2 J-622-NapMeO H F 2-Nap G-1, G-2 C 451 (M⁺ + 1) J-63 1-NapMeO H F 1Me-5-IndG-1, G-2 J-64 2PhBnO H F 1Me-5-Ind G-1, G-2 J-65 4PhBnO H F 1Me-5-IndG-1, G-2 J-66 5OMe-2-IndanO H F 2-Nap G-1, G-2 J-67 5OMe-2-IndanO H F1Me-5-Ind G-1, G-2 J-68 5,6D(OMe)-2-IndanO H F 2-Nap G-1, G-2 J-695,6D(OMe)-2-IndanO H F 1Me-5-Ind G-1, G-2 J-70 5F-2-IndanO H F 2-NapG-1, G-2 J-71 5F-2-IndanO H F 1Me-5-Ind G-1, G-2

TABLE-J-3 J-72

H F 1Me-5-Ind G-1, G-2 J-73

H F 2-Nap G-1, G-2 C 481 (M⁺ + 1) J-74

H F 1Me-5-Ind G-1, G-2 J-75

H F 2-Nap G-1, G-2 J-76

H F 1Me-5-Ind G-1, G-2 J-77

H F 1Me-5-1HIdz G-1, G-2 C 410 (M⁺ + 1) J-78

H F 1Me-5-Ind G-1, G-2 J-79

H F 2-Nap G-1, G-2 J-80

H F 1Me-5-Ind G-1, G-2 J-81

H F 2-Nap G-1, G-2 J-82

H F 1Me-5-Ind G-1, G-2 J-83

H F 1Me-5-Ind G-1, G-2 J-84

H F 1Me-5-Ind G-1, G-2 J-85

H F 1Me-5-Ind G-1, G-2 C 419 (M⁺ + 1) J-86

H F 1Me-5-Ind G-1, G-2 J-87

H F 2-Nap G-1, G-2 J-88

H F 1Me-5-Ind G-1, G-2 J-89

H F 2-Nap G-1, G-2 C 436 (M⁺ + 1) J-90

H F 1Me-5-Ind G-1, G-2 J-91

H F 2-Nap G-1, G-2 J-92

H F 1Me-5-Ind G-1, G-2

Example K-11 Synthesis of methyl3-[3-bromo-4-cyclopentylmethyloxy-5-(naphthalen-2-yl)phenyl]propionate(Compound No. K-11)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 15hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=9:1), Compound No. B-117 (306 mg),2-naphthaleneboronic acid (163 mg), 2 M aqueous sodium carbonate (689μl) and (Ph₃P)₄Pd (74.2 mg) were reacted and treated to obtain the titlecompound (Compound No. K-11, 261 mg).

Synthesis of3-[3-bromo-4-cyclopentylmethyloxy-5-(1H-indol-5-yl)phenyl]propionic acid(Compound No. K-12)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. K-11 (131 mg) and 2 N aqueous sodium hydroxide (400 μl)were reacted and treated to obtain the title compound (Compound No.K-12, 109 mg).

Example K-13 Synthesis of methyl3-[3-bromo-4-cyclopentylmethyloxy-5-(1H-indol-5-yl)phenyl]propionate(Compound No. K-13)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 13hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), Compound No. B-117 (102 mg),5-indoleboronic acid (97 mg), 2 M aqueous sodium carbonate (1.5 ml) and(Ph₃P)₄Pd (46 mg) were reacted and treated to obtain the title compound(Compound No. K-13, 85 mg).

Example K-14 Synthesis of3-[3-bromo-4-cyclopentylmethyloxy-5-(1H-indol-5-yl)phenyl]propionic acid(Compound No. K-14)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. K-13 (85 mg) and 2 N aqueous sodium hydroxide (200 μl) werereacted and treated to obtain the title compound (Compound No. K-14, 79mg).

Example K-17 Synthesis of methyl3-[3-bromo-4-cyclopentyloxy-5-(1-methyl-1H-indazol-5-yl)phenyl]propionate(Compound No. K-17)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 14hours at 80° C., and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=4:1), Compound No. B-118 (306mg), 1-methyl-1H-indazole-5-boronic acid (175 mg), 2 M aqueous sodiumcarbonate (0.68 ml) and (Ph₃P)₄Pd (70.1 mg) were reacted and treated toobtain the title compound (Compound No. K-17, 148 mg).

Examples K-1 to K-40

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-K-1 and Table-K-2.

TABLE-K-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass K-1

Me F 2-Nap G-1 K-2

H F 2-Nap G-2 K-3

Me F 5-Ind G-1 K-4

H F 5-Ind G-2 C 457(M⁺ + 1) K-5

Me F 1Me-5-Ind G-1 K-6

H F 1Me-5-Ind G-2 C 471(M⁺ + 1) K-7

Me F 5-1HIdz G-1 K-8

H F 5-1HIdz G-2 K-9

Me F 1Me-5-1HIdz G-1 K-10

H F 1Me-5-1HIdz G-2 K-11 cPenMeO Me Br 2-Nap K-11 K-12 cPenMeO H Br2-Nap K-12 K-13 cPenMeO Me Br 2-Nap K-13 K-14 cPenMeO H Br 5-Ind Int50,K-13 C 456(M⁺) K-15 cPenO H Br 2-Nap K-11, K-12 K-16 cPenO H Br1Me-5-Ind K-11, K-12 K-17 cPenO Me Br 1Me-5-1HIdz K-11, K-12 K-18 cPenOH Br 1Me-5-1HIdz K-11, K-12 A 4.78 443(M⁺) K-19

H F 2-Nap G-1, G-2 K-20

H F 1Me-5-Ind G-1, G-2 K-21

H F 2-Nap G-1, G-2 K-22

H F 1Me-5-Ind G-1, G-2 K-23

H F 2-Nap G-1, G-2 K-24

H F 1Me-5-Ind G-1, G-2 C 485(M⁺ + 1) K-25

H F 2-Nap G-1, G-2 K-26

H F 1Me-5-Ind G-1, G-2

TABLE-K-2 K-27

H F 2-Nap G-1, G-2 K-28

H F 1Me-5-Ind G-1, G-2 K-29

H F 2-Nap G-1, G-2 K-30

H F 1Me-5-Ind G-1, G-2 K-31

H F 2-Nap G-1, G-2 C 486(M⁺ + 1) K-32

H F 1Me-5-Ind G-1, G-2 K-33

H F 2-Nap G-1, G-2 K-34

H F 1Me-5-Ind G-1, G-2 C 511(M⁺ + 1) K-35

H F 2-Nap G-1, G-2 K-36

H F 1Me-5-Ind G-1, G-2 K-37

H F 2-Nap G-1, G-2 K-38

H F 1Me-5-Ind G-1, G-2 K-39

H F 2-Nap G-1, G-2 K-40

H F 1Me-5-Ind G-1, G-2

Example L-1 Synthesis of3-[4-cyclopentyloxy-3-methyl-5-(naphthalen-2-yl)phenyl]propionic acid(Compound No. L-1)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 6 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=20:1), Compound A-24 (63 mg),2-naphthaleneboronic acid (67 mg), 2 M aqueous sodium carbonate (130 μl)and (Ph₃P)₄Pd (18 mg) were reacted and treated. The obtained substancewas reacted with 2 N aqueous sodium hydroxide μl) and treated accordingto the procedure described in the synthesis method of Intermediate 9 toobtain the title compound (Compound No. L-1, 25 mg).

Example L-2 Synthesis of methyl3-[4-cyclopentyloxy-3-methyl-5-(1-methyl-1H-indazol-5-yl)phenyl]propionate(Compound No. L-2)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 12 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=4:1), Compound No. K-17 (115mg), methylboronic acid (66 mg, Ald), 2 M aqueous sodium carbonate (0.40ml) and (Ph₃P)₄Pd (39.4 mg) were reacted and treated to obtain the titlecompound (Intermediate 52, 84 mg).

Example L-3 Synthesis of3-[4-cyclopentyloxy-3-methyl-5-(1-methyl-1H-indazol-5-yl)phenyl]propionicacid (Compound No. L-3)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 1.5 hours,Compound No. L-2 (82 mg) and 2 N aqueous sodium hydroxide (0.26 ml) werereacted and treated to obtain the title compound (Compound No. L-3, 62mg).

Examples L-1 to L-95

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-L-1 to Table-L-3.

TABLE-L-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass L-1 cPenO H Me 2-Nap L-1 A5.65 375(M⁺ + 1) L-2 cPenO Me Me 1Me-5-1HIdz L-2 L-3 cPenO H Me1Me-5-1HIdz L-3 A 4.50 379(M⁺ + 1) L-4 2EtBuO Me Me 2-Nap L-2 L-5 2EtBuOH Me 2-Nap L-3 C 391(M⁺ + 1) L-6 2EtBuO H Me 6-OMe-2-Nap L-2, L-3 L-72EtBuO Me Me 5-Ind L-2 L-8 2EtBuO H Me 5-Ind L-3 L-9 2EtBuO Me Me1Me-5-Ind L-2 L-10 2EtBuO H Me 1Me-5-Ind L-3 L-11 2EtBuO Me Me 5-1HIdzL-2 L-12 2EtBuO H Me 5-1HIdz L-3 L-13 2EtBuO Me Me 1Me-5-1HIdz L-2 L-142EtBuO H Me 1Me-5-1HIdz L-3 C 395(M⁺ + 1) L-15 2EtBuO Me Me 5-Bzt L-2L-16 2EtBuO H Me 5-Bzt L-3 L-17 2EtBuO Me Me 5-2ABzt L-2 L-18 2EtBuO HMe 5-2ABzt L-3 L-19 2EtBuO Me Me 2Me-5-Bzt L-2 L-20 2EtBuO H Me2Me-5-Bzt L-3 L-21 4Me, chexO H Me 1Me-5-Ind G-1, G-2 L-22

H Me 2-Nap G-1, G-2 L-23 cHepO H Me 2-Nap G-1, G-2 L-24 cHepO H Me1Me-5-Ind G-1, G-2 C 406(M⁺ + 1) L-25 3PhPrO H Me 2-Nap G-1, G-2 L-264PhBuO H Me 1Me-5-Ind G-1, G-2 L-27

H Me 2-Nap G-1, G-2 L-28 1(4MePh)EtO H Me 1Me-5-Ind G-1, G-2 C428(M⁺ + 1) L-29 4ClBnO H Me 2-Nap G-1, G-2 L-30 4CF₃BnO H Me 1Me-5-IndG-1, G-2 L-31 3F, 4(OMe)BnO H Me 2-Nap G-1, G-2 L-32

H Me 1Me-5-Ind G-1, G-2 L-33

H Me 2-Nap G-1, G-2 L-34

H Me 2-Nap G-1, G-2 L-35

H Me 1Me-5-Ind G-1, G-2

TABLE-L-2 L-36

H Me 1Me-5-Ind G-1, G-2 L-37

H Me 1Me-5-Ind G-1, G-2 L-38 1-IndanO H Me 2-Nap G-1, G-2 L-39 2-IndanOH Me 2-Nap G-1, G-2 C 423(M⁺ + 1) L-40 2-IndanO H Me 1Me-5-Ind G-1, G-2L-41 5OMe-2-IndanO H Me 1Me-5-Ind G-1, G-2 L-42 5,6D(OMe)-2-IndanO H Me2-Nap G-1, G-2 L-43 5F-2-IndaneO H Me 2-Nap G-1, G-2 L-44 5F-2-IndaneO HMe 1Me-5-Ind G-1, G-2 L-45

H Me 1Me-5-Ind G-1, G-2 L-46

H Me 2-Nap G-1, G-2 L-47 2(3MePh)EtO H Me 2-Nap G-1, G-2 L-48 2(3FPh)EtOH Me 1Me-5-Ind G-1, G-2 C 432(M⁺ + 1) L-49 2(2ClPh)EtO H Me 1Me-5-IndG-1, G-2 L-50 2(4CF₃Ph)EtO H Me 1Me-5-Ind G-1, G-2 L-51 2(2OMePh)EtO HMe 2-Nap G-1, G-2 C 441(M⁺ + 1) L-52 2(4OMePh)EtO H Me 1Me-5-Ind G-1,G-2 L-53 2(2-Nap)EtO H Me 2-Nap G-1, G-2 L-54 2(2-Nap)EtO H Me 1Me-5-IndG-1, G-2 L-55

H Me 1Me-5-Ind G-1, G-2 L-56

H Me 1Me-5-1HIdz G-1, G-2 C 459(M⁺ + 1) L-57 2(2PhS)EtO H Me 2-Nap G-1,G-2 L-58 3PhPrO H Me 1Me-5-Ind G-1, G-2 L-59 2ClBnO H Me 2-Nap G-1, G-2L-60 2BrBnO H Me 1Me-5-Ind G-1, G-2 L-61 3,5DMeBnO H Me 2-Nap G-1, G-2L-62 4tBuBnO H Me 2-Nap G-1, G-2 L-63 2CF₃BnO H Me 2-Nap G-1, G-2 L-644tBuBnO H Me 1Me-5-Ind G-1, G-2 L-65 4nBuBnO H Me 2-Nap G-1, G-2 C453(M⁺ + 1) L-66 3,5DClBnO H Me 2-Nap G-1, G-2 L-67 2,3DClBnO H Me1Me-5-Ind G-1, G-2 L-68 2-NapMeO H Me 1Me-5-Ind G-1, G-2 L-69 1-NapMeO HMe 2-Nap G-1, G-2 L-70 2PhBnO H Me 1Me-5-Ind G-1, G-2 L-71 4PhBnO H Me2-Nap G-1, G-2 C 476(M⁺ + 1) L-72 5OMe-2-IndanO H Me 1Me-5-Ind G-1, G-2L-73 5F-2-IndaneO H Me 2-Nap G-1, G-2

TABLE-L-3 L-74

H Me 2-Nap G-1, G-2 C 401(M⁺ + 1) L-75

H Me 1Me-5-Ind G-1, G-2 L-76

H Me 2-Nap G-1, G-2 L-77

H Me 1Me-5-Ind G-1, G-2 L-78

H Me 2-Nap G-1, G-2 L-79

H Me 1Me-5-Ind G-1, G-2 L-80

H Me 2-Nap G-1, G-2 L-81

H Me 1Me-5-Ind G-1, G-2 L-82

H Me 2-Nap G-1, G-2 C 412(M⁺ + 1) L-83

H Me 1Me-5-Ind G-1, G-2 L-84

H Me 2-Nap G-1, G-2 L-85

H Me 1Me-5-Ind G-1, G-2 L-86

H Me 2-Nap G-1, G-2 L-87

H Me 1Me-5-Ind G-1, G-2 L-88

H Me 2-Nap G-1, G-2 L-89

H Me 1Me-5-Ind G-1, G-2 C 415(M⁺ + 1) L-90

H Me 2-Nap G-1, G-2 L-91

H Me 1Me-5-Ind G-1, G-2 L-92

H Me 2-Nap G-1, G-2 L-93

H Me 1Me-5-Ind G-1, G-2 C 435(M⁺ + 1) L-94

H Me 2-Nap G-1, G-2 L-95

H Me 1Me-5-Ind G-1, G-2

Examples M-1 to M-32

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification are shown inTable-M-1 and Table-M-2.

TABLE-M-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass M-1

Me Me 2-Nap G-1 C 478(M⁺ + 1) M-2

H Me 2-Nap G-2 C 464(M⁺ + 1) M-3

Me Me 5-Ind G-1 M-4

H Me 5-Ind G-2 M-5

Me Me 1Me-5-Ind G-1 M-6

H Me 1Me-5-Ind G-2 C 467(M⁺ + 1) M-7

Me Me 5-1HIdz G-1 M-8

H Me 5-1HIdz G-2 M-9

Me Me 1Me-5-1HIdz G-1 M-10

H Me 1me-5-1HIdz G-2 M-11

H Me 2-Nap G-1, G-2 C 463(M⁺ + 1) M-12

H Me 1Me-5-Ind G-1, G-2 M-13

H Me 2-Nap G-1, G-2 M-14

H Me 1Me-5-Ind G-1, G-2 C 465(M⁺ + 1) M-15

H Me 2-Nap G-1, G-2 M-16

H Me 1Me-5-Ind G-1, G-2 M-17

H Me 2-Nap G-1, G-2 C 464(M⁺ + 1) M-18

H Me 1Me-5-Ind G-1, G-2 M-19

H Me 2-Nap G-1, G-2 M-20

H Me 1Me-5-Ind G-1, G-2 M-21

H Me 2-Nap G-1, G-2

TABLE-M-2 M-22

H Me 1Me-5-Ind G-1, G-2 M-23

H Me 2-Nap G-1, G-2 M-24

H Me 1Me-5-Ind G-1, G-2 C 486(M⁺ + 1) M-25

H Me 2-Nap G-1, G-2 M-26

H Me 1Me-5-Ind G-1, G-2 M-27

H Me 2-Nap G-1, G-2 M-28

H Me 1Me-5-Ind G-1, G-2 M-29

H Me 2-Nap G-1, G-2 M-30

H Me 1Me-5-Ind G-1, G-2 C 472(M⁺+ 1) M-31

H Me 2-Nap G-1, G-2 M-32

H Me 1Me-5-Ind G-1, G-2

Example N-1 Synthesis of methyl3-{4-[2-(N-acetyl-N-phenylamino)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionate(Compound No. N-1)

A solution of Compound No. G-107 (32 mg) in methylene chloride (1 ml)was added with pyridine (24 μl, TCI) and acetyl chloride (21 μl, TCI),and stirred for 17 hours. The reaction mixture was added with water (3ml), and extracted with methylene chloride (10 ml). The organic layerwas washed with saturated brine and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate 2:1) to obtain the titlecompound (Compound No. N-1, 28.1 mg).

Example N-2 Synthesis of3-{4-[2-(N-acetyl-N-phenylamino)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionicacid (Compound No. N-2)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. N-1 (28 mg) and 2 N aqueous sodium hydroxide (0.25 ml) werereacted and treated to obtain the title compound (Compound No. N-2, 22mg).

Example N-29 Synthesis of methyl3-{4-[2-(N-methoxycarbonyl-N-phenylamino)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionate(Compound No. N-29)

According to the procedure described in the synthesis method of CompoundNo. N-1, Compound No. G-107 (32 mg), pyridine (23 μl) and methylchloroformate (23 μl, TCI) were reacted and treated to obtain the titlecompound (Compound No. N-29, 17.3 mg).

Example N-30 Synthesis of3-{4-[2-(N-methoxycarbonyl-N-phenylamino)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionicacid (Compound No. N-30)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. N-29 (17 mg) and 2 N aqueous sodium hydroxide (0.25 ml)were reacted and treated to obtain the title compound (Compound No.N-30, 10.1 mg).

Example N-48 Synthesis of methyl3-{4-[2-(N-methylsulfonyl-N-phenylamino)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionate(Compound No. N-48)

According to the procedure described in the synthesis method of CompoundNo. N-1, Compound No. G-107 (32 mg), pyridine (24 μl) andmethanesulfonyl chloride (23 μl) were reacted and treated to obtain thetitle compound (Compound No. N-48, 32.3 mg).

Example N-49 Synthesis of3-{4-[2-(N-methylsulfonyl-N-phenylamino)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionicacid (Compound No. N-49)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. N-48 (32 mg) and 2 N aqueous sodium hydroxide (0.25 ml)were reacted and treated to obtain the title compound (Compound No.N-49, 17 mg).

Example N-55 Synthesis of methyl3-{4-[2-(3-ethyl-1-phenylureido)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionate(Compound No. N-55)

According to the procedure described in the synthesis method of CompoundNo. N-1 provided that the reaction was carried out for 41 hours,Compound No. G-107 (32 mg), pyridine (24 μl) and ethyl isocyanate (24μl, Nakarai Tecs) were reacted and treated to obtain the title compound(Compound No. N-55, 31.2 mg).

Example N-56 Synthesis of3-{4-[2-(3-ethyl-1-phenylureido)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionicacid (Compound No. N-56)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. N-55 (31 mg) and 2 N aqueous sodium hydroxide (0.25 ml)were reacted and treated to obtain the title compound (Compound No.N-56, 15 mg).

Example N-64 Synthesis of methyl3-{4-[2-(3-ethyl-1-phenylthioureido)ethyloxy]-3(naphthalen-2-yl)phenyl}propionate (Compound No. N-64)

According to the procedure described in the synthesis method of CompoundNo. N-1 provided that the reaction was carried out for 41 hours,Compound No. G-107 (32 mg), pyridine (24 μl) and ethyl isothiocyanate(21 μl, Nakarai Tecs) were reacted and treated to obtain the titlecompound (Compound No. N-64, 27.4 mg).

Example N-65 Synthesis of3-{4-[2-(3-ethyl-1-phenylthioureido)ethyloxy]-3-(naphthalen-2-yl)phenyl}propionicacid (Compound No. N-65)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. N-64 (27 mg) and 2 N aqueous sodium hydroxide (0.25 ml)were reacted and treated to obtain the title compound (Compound No.N-65, 8.9 mg).

Examples N-1 to N-74

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-N-1 and Table-N-2.

TABLE-N-1

LCMS Exp. A⁵Re Y Zx AR Syn method RTime Mass N-1 COMe Me H 2-Nap N-1 N-2COMe H H 2-Nap N-2 N-3 COMe Me H 5-Ind N-1 N-4 COMe H H 5-Ind N-2 C457(M⁺ + 1) N-5 COMe Me H 1Me-5-Ind N-1 N-6 COMe H H 1Me-5-Ind N-2 N-7COMe Me H 5-1HIdz N-1 N-8 COMe H H 5-1HIdz N-2 N-9 COMe Me H 1Me-5-1HIdzN-1 N-10 COMe H H 1Me-5-1HIdz N-2 N-11 COPh H H 2-Nap N-1, N-2 C516(M⁺ + 1) N-12 COPh H H 1Me-5-Ind N-1, N-2 N-13 COtBu H H 2-Nap N-1,N-2 N-14 COtBu H H 1Me-5-Ind N-1, N-2 N-15 COiPr H H 2-Nap N-1, N-2 C496(M⁺ + 1) N-16 COiPr H H 1Me-5-Ind N-1, N-2 N-17 COCH(Et)nBu H H 2-NapN-1, N-2 N-18 COCH(Et)nBu H H 1Me-5-Ind N-1, N-2 N-19 COCH₂OMe H H 2-NapN-1, N-2 N-20 COCH₂OMe H H 1Me-5-Ind N-1, N-2 N-21 COCH═CHMe H H 2-NapN-1, N-2 N-22 COCH═CHMe H H 1Me-5-Ind N-1, N-2 C 483(M⁺ + 1) N-23 COiBuH H 2-Nap N-1, N-2 N-24 COiBu H H 1Me-5-Ind N-1, N-2 N-25 COcPr H H2-Nap N-1, N-2 N-26 COcPr H H 1Me-5-Ind N-1, N-2 C 483(M⁺ + 1) N-27CO(CH₂)₂cPen H H 2-Nap N-1, N-2 N-28 CO(CH₂)₂cPen H H 1-Me-5-Ind N-1,N-2 N-29 COOMe Me H 2-Nap N-29 N-30 COOMe H H 2-Nap N-30 N-31 COOMe H H1Me-5-Ind N-29, N-30 N-32 COOPh H H 2-Nap N-29, N-30 C 516(M⁺ + 1) N-33COOPh H H 1Me-5-Ind N-29, N-30 N-34 CONMe₂ H H 2-Nap N-29, N-30 C483(M⁺ + 1) N-35 CONMe H H 1Me-5-Ind N-29, N-30 N-36 COOiBu H H 2-NapN-29, N-30 N-37 COOiBu H H 1Me-5-Ind N-29, N-30 N-38 C(O)SMe H H 2-NapN-29, N-30 N-39 C(O)SMe H H 1Me-5-Ind N-29, N-30 N-40

H H 2-Nap N-29, N-30 N-41

H H 1Me-5-Ind N-29, N-30 C 528(M⁺ + 1)

TABLE-N-2 N-42

H H 2-Nap Int53, N-29 N-43

H H 1Me-5-Ind Int53, N-29 N-44 COO(CH₂)₂OMe H H 2-Nap Int53, N-29 N-45COO(CH₂)₂OMe H H 1Me-5-Ind Int53, N-29 N-46

H H 2-Nap Int53, N-29 N-47

H H 1Me-5-Ind Int53, N-29 N-48 SO₂Me Me H 2-Nap N-48 N-49 SO₂Me H H2-Nap N-49 N-50 SO₂Me H H 1Me-5-Ind N-48, N-49 C 493(M⁺ + 1) N-51 SO₂PhH H 2-Nap N-48, N-49 N-52 SO₂Ph H H 1Me-5-Ind N-48, N-49 N-53 SO₂NMe₂ HH 2-Nap N-48, N-49 C 519(M⁺ + 1) N-54 SO₂NMe₂ H H 1Me-5-Ind N-48, N-49N-55 CONHEt Me H 2-Nap N-55 N-56 CONHEt H H 2-Nap N-56 C 483(M⁺ + 1)N-57 CONHEt H H 1Me-5-Ind N-55, N-56 N-58 CONHPh H H 2-Nap N-55, N-56N-59 CONHPh H H 1Me-5-Ind N-55, N-56 N-60 CONHcHex H H 2-Nap N-55, N-56N-61 CONHcHex H H 1Me-5-Ind N-55, N-56 C 540(M⁺ + 1) N-62 CONHBn H H2-Nap N-55, N-56 N-63 CONHBn H H 1Me-5-Ind N-55, N-56 N-64 CSNHMe Me H2-Nap N-64 N-65 CSNHMe H H 2-Nap N-65 N-66 CSNHMe H H 1Me-5-Ind N-64,N-65 N-67 CSNHPh H H 2-Nap N-64, N-65 N-68 CSNHPh H H 1Me-5-Ind N-64,N-65 N-69 CSNHPh(3-Py) H H 2-Nap N-64, N-65 C 548(M⁺ + 1) N-70CSNHPh(3-Py) H H 1Me-5-Ind N-64, N-65 N-71 CSNHiPr H H 2-Nap N-64, N-65N-72 CSNHiPr H H 1Me-5-Ind N-64, N-65 C 516(M⁺ + 1) N-73 CSNHBn H H2-Nap N-64, N-65 N-74 CSNHBn H H 1Me-5-Ind N-64, N-65

Example P-1 Synthesis of ethyl3-[2-cyclopentylmethyloxy-3-(naphthalen-2-yl)pyridin-5-yl]propionate(Compound No. P-1)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 14hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), 2-naphthaleneboronic acid (119 mg),Compound No. E-1 (83 mg), 2 M aqueous sodium carbonate (0.3 ml) and(Ph₃P)₄Pd (38.1 mg) were reacted and treated to obtain the titlecompound (Compound No. P-1, 76 mg).

Example P-2 Synthesis of3-[2-cyclopentylmethyloxy-3-(naphthalen-2-yl)pyridin-5-yl]propionic acid(Compound No. P-2)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. P-1 (47.8 mg) and 2 N aqueous sodium hydroxide (0.2 ml)were reacted and treated to obtain the title compound (Compound No. P-2,20 mg).

Example P-36 Synthesis of ethyl3-{3-(naphthalen-2-yl)-2-[(R)-1-phenylethyloxy]pyridin-5-yl}propionate(Compound No. P-36)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 2hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=6:1), 2-naphthaleneboronic acid (44 mg),Compound No. E-7 (73.3 mg), 2 M aqueous sodium carbonate (120 μl) and(Ph₃P)₄Pd (21.3 mg) were reacted and treated to obtain the titlecompound (Compound No. P-36, 44 mg).

Example P-37 Synthesis of3-{3-(naphthalen-2-yl)-2-[(R)-1-phenylethyloxy]pyridin-5-yl}propionicacid (Compound No. P-37)

According to the procedure described in the synthesis method ofIntermediate 9, Compound No. P-36 (41.2 mg) and 2 N aqueous sodiumhydroxide (0.1 ml) were reacted and treated to obtain the title compound(Compound No. P-37, 38 mg).

Example P-42 Synthesis of ethyl3-{3-(naphthalen-2-yl)-2-[4-(trifluoromethyl)phenylmethyloxy]pyridin-5-yl}propionate(Compound No. P-42)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 2hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=6:1), 2-naphthaleneboronic acid (37.4 mg),Compound No. E-13 (42.4 mg), 2 M aqueous sodium carbonate (90 μl) and(Ph₃P)₄Pd (21.4 mg) were reacted and treated to obtain the titlecompound (Compound No. P-42, 30.4 mg).

Example P-43 Synthesis of3-{3-(naphthalen-2-yl)-2-[4-(trifluoromethyl)phenylmethyloxy]pyridin-5-yl}propionicacid (Compound No. P-43)

According to the procedure described in the synthesis method ofIntermediate 9, Compound No. P-42 (29.5 mg) and 2 N aqueous sodiumhydroxide (0.15 ml) were reacted and treated to obtain the titlecompound (Compound No. P-43, 24.1 mg).

Examples P-1 to P-50

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-P-1 and Table-P-2.

TABLE P-1

LCMS Exp. RxO Y AR Syn method RTime Mass P-1 cPenMeO Et 2-Nap P-1 P-2cPenMeO H 2-Nap P-2 A 5.60 376 (M⁺ + 1) P-3 cPenMeO Et 5-Ind P-1 A 5.37393 (M⁺ + 1) P-4 cPenMeO H 5-Ind P-2 P-5 cPenMeO Et 1Me-5-Ind P-1 P-6cPenMeO H 1Me-5-Ind P-2 A 4.90 379 (M⁺ + 1) P-7 cPenMeO Et 1Me-5-Ind P-1P-8 cPenMeO H 5-1HIdz P-2 P-9 cPenMeO Et 5-1HIdz P-1 P-10 cPenMeO H1Me-5-1HIdz P-2 P-11 cPenMeO Et 5-Bzt P-1 P-12 cPenMeO H 5-Bzt P-2 P-13cPenMeO Et 5-2ABzt P-1 P-14 cPenMeO H 5-2ABzt P-2 P-15 cPenMeO H 6-IQP-1, P-2 C 377 (M⁺ + 1) P-16 cPenO H 2-Nap P-1, P-2 P-17 cPenO H 5-IndP-1, P-2 C 351 (M⁺ + 1) P-18 cPenO H 1Me-5-Ind P-1, P-2 P-19 cPenO H5-1HIdz P-1, P-2 P-20 cPenO H 1Me-5-1HIdz P-1, P-2 P-21 cPenO H 5-BztP-1, P-2 P-22 cPenO H 5-2ABzt P-1, P-2 P-23 cHexO H 2-Nap P-1, P-2 A5.51 376 (M⁺ + 1) P-24 cHexO H 5-Ind P-1, P-2 P-25 cHexO H 1Me-5-IndP-1, P-2 P-26 cHexO H 1Me-5-1HIdz P-1, P-2 P-27 2EtBuO H 2-Nap P-1, P-2A 5.68 378 (M⁺ + 1) P-28 2EtBuO H 5-Ind P-1, P-2 P-29 2EtBuO H 1Me-5-IndP-1, P-2 P-30 iBuO H 2-Nap P-1, P-2 A 5.13 350 (M⁺ + 1) P-31 iBuO H5-Ind P-1, P-2 P-32 iBuO H 1Me-5-Ind P-1, P-2 P-33 iBuO H 1Me-5-1HIdzP-1, P-2 P-34 BnO H 2-Nap P-1, P-2 P-35 BnO H 1Me-5-Ind P-1, P-2 P-36(R)1PhEtO Et 2-Nap P-36 P-37 (R)1PhEtO H 2-Nap P-37 P-38 (S)1PhEtO H2-Nap P-36, P37 A 5.31 398 (M⁺ + 1) P-39 (S)1PhEtO H 1Me-5-Ind P-36, P37A 4.75 401 (M⁺ + 1) P-40 2MeBnO H 2-Nap P-1, P-2 P-41 2MeBnO H 1Me-5-IndP-1, P-2

TABLE P-2 P-42 4CF3BnO Et 2-Nap P-42 P-43 4CF3BnO H 2-Nap P-43 A 5.52452 (M⁺ + 1) P-44 4CF3BnO H 1Me-5-Ind P-1, P-2 P-45 3PhBuO H 1Me-5-IndP-1, P-2 P-46 2(2-Nap)EtO H 2-Nap P-1, P-2 P-47 2(2-Nap)EtO H 1Me-5-IndP-1, P-2 P-48 2(2FPh)EtO H 2-Nap P-1, P-2 P-49 2(2FPh)EtO H 5-Ind P-1, A4.18 405 (M⁺ + 1) P-2 P-50 2(2FPh)EtO H 1Me-5-Ind P-1, P-2

Example Q-1 Synthesis of methyl3-[4-methoxy-3-(naphthalen-2-yl)-5-nitrophenyl]propionate (Intermediate49)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 15 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=10:1), Intermediate 21 (2.65g), 2-naphthaleneboronic acid (2.87 g), 2 M aqueous sodium carbonate(7.5 ml) and (Ph₃P)₄Pd (960 mg) were reacted and treated to obtain thetitle compound (Intermediate 49, 2.47 g).

Synthesis of 3-[4-methoxy-3-(naphthalen-2-yl)-5-nitrophenyl]propionicacid (Intermediate 50)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 40minutes, Intermediate 49 (2.45 g) and 2 N aqueous sodium hydroxide (6.7ml) were reacted and treated to obtain the title compound (Intermediate60, 1.96 g).

Synthesis of methyl3-[4-hydroxy-3-(naphthalen-2-yl)-5-nitrophenyl]propionate (Intermediate51)

According to the procedure described in the synthesis method ofIntermediate 10 provided that the reaction was carried out for 3 hours,pyridine (10 ml), concentrated hydrochloric acid (10 ml), andIntermediate 50 (1.00 g) were reacted and treated to obtain crude powdersubstance. This substance was reacted with thionyl chloride (282 μl) inmethanol and treated according to the procedure described in thesynthesis method of Intermediate 1 to obtain the title compound(Intermediate 51, 306 mg).

Synthesis of methyl3-[4-cyclopentyloxy-3-(naphthalen-2-yl)-5-nitrophenyl]propionate(Compound No. Q-1)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for15.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=19:1), Intermediate 51 (84 mg), Ph₃P (125mg), cyclopentanol (50 μl) and 40% DIAD (224 μl) were reacted andtreated to obtain the title compound (Compound No. Q-1, 90 mg).

Example Q-2 Synthesis of methyl3-[3-amino-4-cyclopentyloxy-5-(naphthalen-2-yl)phenyl]propionate(Compound No. Q-2)

A solution of Compound No. Q-1 (59.1 mg) in methanol (5 ml) was addedwith platinum oxide (5 mg, Ald), and stirred at room temperature for 30minutes under hydrogen atmosphere. The reaction mixture was filtered,and the solvent of the filtrate was evaporated under reduced pressure.The residue was purified by column chromatography (Quad, hexane:ethylacetate=4:1) to obtain the title compound (Compound No. Q-2, 49 mg).

Example Q-3 Synthesis of3-[3-amino-4-cyclopentyloxy-5-(naphthalen-2-yl)phenyl]propionic acid(Compound No. Q-3)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. Q-2 (40 mg) and 2 N aqueous sodium hydroxide (150 μl) werereacted and treated to obtain the title compound (Compound No. Q-3, 38mg).

Example Q-4 Synthesis of methyl3-[4-cyclopentyloxy-3-(1H-indol-5-yl)-5-nitrophenyl]propionate (CompoundNo. Q-4)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 16 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=4:1), Compound No. A-28 (187mg), 5-indoleboronic acid (143 mg), 2 M aqueous sodium carbonate (400μl) and (Ph₃P)₄Pd (51 mg) were reacted and treated to obtain the titlecompound (Compound No. Q-4, 192 mg).

Example Q-5 Synthesis of methyl3-[3-amino-4-cyclopentyloxy-5-(1H-indol-5-yl)phenyl]propionate (CompoundNo. Q-5)

According to the procedure described in the synthesis method of CompoundNo. Q-2 with the modification that the purification was performed bycolumn chromatography (Quad, hexane:ethyl acetate=2:1), Compound No. Q-4(59.1 mg) and platinum oxide (5 mg) were reacted and treated to obtainthe title compound (Compound No. Q-5, 49.3 mg).

Example Q-6 Synthesis of3-[3-amino-4-cyclopentyloxy-5-(1H-indol-5-yl)phenyl]propionic acid(Compound No. Q-6)

According to the procedure described in the synthesis method ofIntermediate 9, Compound No. Q-5 (44 mg) and 2 N aqueous sodiumhydroxide (150 μl) were reacted and treated to obtain the title compound(Compound No. Q-6, 41 mg).

Example Q-8 Synthesis of methyl3-[4-cyclopentyloxy-3-(1-methyl-1H-indazol-5-yl)-5-nitrophenyl]propionate(Compound No. Q-8)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 16 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=3:1), Compound No. A-28 (182mg), 1-methyl-5-indazoleboronic acid (152 mg), 2 M aqueous sodiumcarbonate (400 μl) and (Ph₃P)₄Pd (58.9 mg) were reacted and treated toobtain the title compound (Compound No. Q-8, 181 mg).

Example Q-9 Synthesis of methyl3-[3-amino-4-cyclopentyloxy-5-(1-methyl-1H-indazol-5-yl)phenyl]propionicacid (Compound No. Q-9)

A solution of Compound No. Q-8 (578 mg) in a mixture of ethyl acetate (2ml) and methanol (5 ml) was added with Raney 2800 nickel (230 mg) andstirred at room temperature for 6 hours under hydrogen atmosphere. Thereaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=2:1) to obtain the titlecompound (Compound No. Q-9, 484 mg).

Example Q-10 Synthesis of3-[3-amino-4-cyclopentyloxy-5-(1H-indazol-5-yl)phenyl]propionic acid(Compound No. Q-10)

According to the procedure described in the synthesis method ofIntermediate 9, Compound No. Q-9 (56 mg) and 2 N aqueous sodiumhydroxide (200 μl) were reacted and treated to obtain the title compound(Compound No. Q-10, 50 mg).

Example Q-47 Synthesis of methyl3-[4-benzyloxy-3-(naphthalen-2-yl)-5-nitrophenyl]propionate (CompoundNo. Q-47)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 12 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=8:1), Compound No. B-95 (6.00g), 2-naphthaleneboronic acid (4.11 g), 2 M aqueous sodium carbonate(13.5 ml) and (Ph₃P)₄Pd (1.36 g) were reacted and treated to obtain thetitle compound (Compound No. Q-47, 5.81 g).

Example Q-48 Synthesis of methyl3-[3-amino-4-benzyloxy-5-(naphthalen-2-yl)phenyl]propionate (CompoundNo. Q-48)

According to the procedure described in the synthesis method of CompoundNo. Q-9 with the modifications that the reaction was carried out for 20hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=2:1), Compound No. Q-47 (5.04 g) and Raney2800 nickel (2.50 g) were reacted and treated to obtain the titlecompound (Compound No. Q-48, 4.21 g).

Example Q-1 to Q-52

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-Q-1.

TABLE Q-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass Q-1 cPenO Me NO2 2-Nap Q-1Q-2 cPenO Me NH2 2-Nap Q-2 Q-3 cPenO H NH2 2-Nap Q-3 A 4.78 376 (M⁺ + 1)Q-4 cPenO Me NO2 5-Ind Q-4 Q-5 cPenO Me NH2 5-Ind Q-5 Q-6 cPenO H NH25-Ind Q-6 A 3.75 365 (M⁺ + 1) Q-7 cPenO H NH2 1Me-5-Ind Q-4, Q-5, Q-6 A4.19 379 (M⁺ + 1) Q-8 cPenO Me NO2 1Me-5-1HIdz Q-8 Q-9 cPenO Me NH21Me-5-1HIdz Q-9 Q-10 cPenO H NH2 1Me-5-1HIdz Q-10 Q-11 cPenO H NH25-1HIdz Q-8, Q-9, Q-10 Q-12 cPenO H NH2 5-Bzt Q-8, Q-9, Q-10 Q-13 cPenOH NH2 5-2ABzt Q-8, Q-9, Q-10 Q-14 cPenO H NH2 2Me-5-Bzt Q-8, Q-9, Q-10Q-15 cHexO H NH2 2-Nap Q-1, Q-2, Q-3 A 5.66 404 (M⁺ + 1) Q-16 cHexO HNH2 1Me-5-Ind Q-4, Q-5, Q-6 Q-17 cHexO H NH2 1Me-5-1HIdz Q-8, Q-9, Q-10Q-18 2EtBuO H NH2 2-Nap Q-1, Q-2, Q-3 Q-19 2EtBuO H NH2 5-Ind Q-4, Q-5,Q-6 A 4.26 381 (M⁺ + 1) Q-20 2EtBuO H NH2 1Me-5-Ind Q-4, Q-5, Q-6 Q-212EtBuO H NH2 5-1HIdz Q-8, Q-9, Q-10 Q-22 2EtBuO H NH2 1Me-5-1HIdz Q-8,Q-9, Q-10 Q-23 2EtBuO H NH2 5-Bzt Q-8, Q-9, Q-10 Q-24 2EtBuO H NH25-2ABzt Q-8, Q-9, Q-10 Q-25 2EtBuO H NH2 2Me-5-Bzt Q-8, Q-9, Q-10 Q-26iBuO H NH2 2-Nap Q-1, Q-2, Q-3 A 4.82 364 (M⁺ + 1) Q-27 iBuO H NH21Me-5-Ind Q-4, Q-5, Q-6 Q-28 iBuO H NH2 1Me-5-1HIdz Q-8, Q-9, Q-10 A3.66 368 (M⁺ + 1) Q-29 (S)1PhEtO H NH2 2-Nap Q-1, Q-2, Q-3 A 4.87 412(M⁺ + 1) Q-30 (S)1PhEtO H NH2 1Me-5-Ind Q-4, Q-5, Q-6 A 4.31 415(M⁺ + 1) Q-31 (S)1PhEtO H NH2 1Me-5-1HIdz Q-8, Q-9, Q-10 A 3.76 416(M⁺ + 1) Q-32 4CF₃BnO H NH2 2-Nap Q-1, Q-2, Q-3 A 5.26 466 (M⁺ + 1) Q-334CF₃BnO H NH2 1Me-5-Ind Q-4, Q-5, Q-6 A 4.20 455 (M⁺ + 1) Q-34 4CF₃BnO HNH2 1Me-5-1HIdz Q-8, Q-9, Q-10 Q-35 2-IndanO H NH2 2-Nap Q-1, Q-2, Q-3 A5.10 424 (M⁺ + 1) Q-36 2-IndanO H NH2 1Me-5-Ind Q-4, Q-5, Q-6 A 4.63 427(M⁺ + 1) Q-37 2-IndanO H NH2 1Me-5-1HIdz Q-8, Q-9, Q-10 A 4.14 428(M⁺ + 1) Q-38 5OMe-2-IndanO H NH2 2-Nap Q-1, Q-2, Q-3 Q-395,6(OMe)-2-IndanO H NH2 1Me-5-Ind Q-4, Q-5, Q-6 Q-40 5F-2-IndanO H NH21Me-5-1HIdz Q-8, Q-9, Q-10 Q-41 2(4FPh)EtO H NH2 2-Nap Q-1, Q-2, Q-3Q-42 2(4FPh)EtO H NH2 1Me-5-Ind Q-4, Q-5, Q-6 Q-43 2(4FPh)EtO H NH21Me-5-1HIdz Q-8, Q-9, Q-10 A 4.48 448 (M⁺ + 1) Q-44 2(4DMAPh)EtO H NH22-Nap Q-1, Q-2, Q-3 A 4.28 455 (M⁺ + 1) Q-45 2(4DMAPh)EtO H NH21Me-5-Ind Q-4, Q-5, Q-6 Q-46 2(4DMAPh)EtO H NH2 1Me-5-1HIdz Q-8, Q-9,Q-10 A 3.12 459 (M⁺ + 1) Q-47 BnO Me NO2 2-Nap Q-47 Q-47 Q-48 BnO Me NH22-Nap Q-48 Q-48 Q-49 BnO H NH2 2-Nap Q-3 Q-50 BnO Me NO2 1Me-5-1HIdzQ-47 Q-51 BnO Me NH2 1Me-5-1HIdz Q-48 Q-52 BnO H NH2 1Me-5-1HIdz Q-10

Example S-1 Synthesis of methyl3-{4-benzyloxy-3-(naphthalen-2-yl)-5-[N-(2,2,2-trifluoroacetyl)amino]phenyl}propionate(Intermediate 52)

According to the procedure described in the synthesis method of CompoundNo. B-103 with the modifications that the reaction was carried out for1.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=4:1), Compound No. Q-48 (4.18 g),triethylamine (4.65 ml) and trifluoroacetic anhydride (7.40 ml) werereacted and treated to obtain the title compound (Intermediate 52, 4.72g).

Synthesis of methyl3-{4-hydroxy-3-(naphthalen-2-yl)-5-[N-(2,2,2-trifluoroacetyl)amino]phenyl}propionate(Intermediate 53)

A solution of Intermediate 52 (3.20 g) in a mixture of ethyl acetate (50ml) and methanol (25 ml) was added with 10% palladium/carbon (98 mg),and stirred at room temperature for 2 hours under hydrogen atmosphere.The reaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure to obtain the title compound(Intermediate 53, 2.39 g).

Synthesis of methyl3-{4-cyclopentyloxy-3-(naphthalen-2-yl)-5-[N-(2,2,2-trifluoroacetyl)amino]phenyl}propionate(Intermediate 54)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for15.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=19:1), Intermediate 53 (84 mg), Ph₃P (125mg), cyclopentanol (50 μl) and 40% DIAD (224 μl) were reacted andtreated to obtain the title compound (Intermediate 54, 90 mg).

Synthesis of methyl3-{4-cyclopentyloxy-3-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]-5-(naphthalen-2-yl)phenyl}propionate(Intermediate 55)

A solution of Intermediate 54 (208 mg) in DMF (5 ml) was added with 60%sodium hydride (21 mg) under ice cooling, and stirred for 20 minutes.This reaction mixture was added dropwise with methyl iodide (150 μl),stirred for 10 minutes, then warmed to room temperature, and furtherstirred for 1 hour. The reaction mixture was poured into ice water, andethyl acetate (100 ml) was added for extraction. The organic layer wassuccessively washed with saturated aqueous sodium hydrogencarbonate,saturated aqueous ammonium chloride, and saturated brine and dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by column chromatography (Quad, hexane:ethyl acetate=5:1) toobtain the title compound (Intermediate 55, 200 mg).

Synthesis of3-[4-cyclopentyloxy-3-(N-methylamino)-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-1)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 6 hours,Intermediate 55 (198 mg) and 2 N aqueous sodium hydroxide (800 μl) werereacted and treated to obtain the title compound (Compound No. S-1, 38mg).

Example S-3 Synthesis of methyl3-[3-acetylamino-4-cyclopentyloxy-5-(naphthalen-2-yl)phenyl]propionate(Compound No. S-3)

A solution of Compound No. Q-2 (81 mg) in methylene chloride (2 ml) wasadded with N-methylmorpholine (33 μl, WAKO), and added with acetylchloride (22 μl) under ice cooling. The reaction mixture was stirred for10 minutes, then warmed to room temperature, and further stirred for 18hours. The reaction mixture was poured into aqueous sodiumhydrogencarbonate (100 ml), and added with ethyl acetate (150 ml) forextraction. The organic layer was successively washed with saturatedaqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride,and saturated brine and dried, and then the solvent was evaporated underreduced pressure. The residue was purified by column chromatography(Quad, hexane:ethyl acetate 6:1) to obtain the title compound (CompoundNo. S-3, 85 mg).

Example S-4 Synthesis of3-[3-acetylamino-4-cyclopentylmethyloxy-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-4)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 15 hours,Compound No. S-3 (80 mg) and 2 N aqueous sodium hydroxide (400 μl) werereacted and treated to obtain the title compound (Compound No. S-4, 75mg).

Example S-5 Synthesis of3-[4-cyclopentyloxy-3-formylamino-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-5)

A solution of Compound No. Q-2 (90 mg) in DMF (5 ml) was added with amixture of formic acid (200 μl) and acetic anhydride (100 μl) under icecooling. The reaction mixture was stirred 10 minutes, then warmed toroom temperature, and further stirred for 18 hours. The reaction mixturewas poured into aqueous sodium hydrogencarbonate (100 ml), and addedwith ethyl acetate (150 ml) for extraction. The organic layer wassuccessively washed with saturated aqueous sodium hydrogencarbonate,saturated aqueous ammonium chloride, and saturated brine and dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by column chromatography (Quad, hexane:ethyl acetate=5:1). Theobtained substance was reacted and treated with 2N aqueous sodiumhydroxide (400 μl) according to the procedure described in the synthesismethod of Intermediate 9 to obtain the title compound (Compound No. S-5,65 mg).

Example S-6 Synthesis of methyl3-[3-(2-acetoxyacetylamino)-4-cyclopentyloxy-5-(naphthalen-2-yl)phenyl]propionate(Compound No. S-6)

According to the procedure described in the synthesis method ofIntermediate 70, Compound No. Q-2 (88 mg), N-methylmorpholine (36 μl)and acetoxyacetyl chloride (35 μl, Ald) were reacted and treated toobtain the title compound (Compound No. S-6, 75 mg).

Example S-7 Synthesis of3-[4-cyclopentyloxy-3-(2-hydroxyacetylamino)-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-7)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 15.5hours, Compound No. S-6 (102 mg) and 2 N aqueous sodium hydroxide (500μl) were reacted and treated to obtain the title compound (Compound No.S-7, 80 mg).

Example S-8 Synthesis of3-[3-carbamoylamino-4-cyclopentyloxy-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-8)

A solution of Compound No. Q-2 (100 mg) in a mixture of acetic acid (2ml) and purified water (0.4 ml) was added with potassium cyanate (45 mg,Wako Pure Chemical Industries), and stirred at room temperature for 1hour. The reaction mixture was poured into water (50 ml) containing ice,and extracted with isopropyl ether (150 ml×2). The organic layer wassuccessively washed with saturated aqueous sodium hydrogencarbonate,saturated aqueous ammonium chloride, and saturated brine and dried, andthen the solvent was evaporated under reduced pressure. The obtainedsubstance was reacted with 2 N aqueous sodium hydroxide (300 μl) andtreated according to the procedure described in the synthesis method ofIntermediate 9 to obtain the title compound (Compound No. S-8, 70 mg).

Example S-9 Synthesis of methyl3-[4-cyclopentyloxy-3-methylsulfonylamino-5-(naphthalen-2-yl)phenyl]propionate(Compound No. S-9)

A solution of Compound No. Q-2 (81 mg) in methylene chloride (2 ml) wasadded with pyridine (300 μl), and then added with methanesulfonylchloride (40 μl) under ice cooling. The reaction mixture was stirred for10 minutes, then warmed to room temperature, and further stirred for 2hours. The reaction mixture was poured into 1 N hydrochloric acid, andadded with ethyl acetate (150 ml) for extraction. The organic layer waswashed successively with saturated aqueous sodium hydrogencarbonate, andsaturated brine, and dried, and then the solvent of the organic layerwas evaporated under reduced pressure. The residue was purified bycolumn chromatography (Quad, hexane:ethyl acetate=13:2) to obtain thetitle compound (Compound No. S-9, 96 mg).

Synthesis of3-[4-cyclopentyloxy-3-methylsulfonylamino-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-10)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out at roomtemperature for 17.5 hours and at 60° C. for 3 hours, Compound No. S-9(81 mg) and 2 N aqueous sodium hydroxide (400 μl) were reacted andtreated to obtain the title compound (Compound No. S-10, 80 mg).

Example S-11 Synthesis of3-[4-cyclopentyloxy-3-(N,N-dimethylsulfamoylamino)-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-11)

A solution of Compound No. Q-2 (163 mg) in pyridine (5 ml) wassuccessively added with 4-dimethylaminopyridine (104 mg, TCI) anddimethylsulfamoyl chloride (520 μl, TCI), and stirred for 5 days. Thereaction mixture was added with water (30 ml) and ethyl acetate (90 ml)for extraction. The organic layer was washed with saturated brine anddried, and then the solvent was evaporated under reduced pressure. Theresidue was purified by column chromatography (Quad, hexane:ethylacetate=6:1). The obtained substance was reacted with 2 N aqueous sodiumhydroxide (300 μl) and treated according to the procedure described inthe synthesis method of Intermediate 9 to obtain the title compound(Compound No. S-11, 105 mg).

Example S-12 Synthesis of3-[4-cyclopentyloxy-3-(N,N-dimethylamino)-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. S-12)

A solution of Compound No. Q-2 (60 mg) in DMF (3 ml) was added with 60%sodium hydride (26 mg) under ice cooling, and stirred for 10 minutes.The reaction mixture was added with methyl iodide (100 μl), stirred for10 minutes, then warmed to 60° C., and further stirred for 2 hours. Thereaction mixture was poured into water (20 ml), and ethyl acetate (50ml) was added for extraction. The organic layer was successively washedwith saturated aqueous sodium hydrogencarbonate, saturated aqueousammonium chloride, and saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was purified bycolumn chromatography (Quad, hexane:ethyl acetate=8:1). The obtainedsubstance was reacted with 2 N aqueous sodium hydroxide (150 μl) andtreated according to the procedure described in the synthesis method ofIntermediate 9 to obtain the title compound (Compound No. S-12, 46 mg).

Synthesis of methyl3-{4-benzyloxy-3-(1-methyl-1H-indazol-5-yl)-5-[N-(2,2,2-trifluoroacetyl)amino]phenyl}propionate(Intermediate 56)

According to the procedure described in the synthesis method of CompoundNo. B-103 with the modifications that the reaction was carried out for1.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=3:1), Compound No. Q-51 (2.09 g),triethylamine (3.70 ml) and trifluoroacetic anhydride (2.35 ml) werereacted and treated to obtain the title compound (Intermediate 56, 2.36g).

Synthesis of methyl3-{4-hydroxy-3-(1-methyl-1H-indazol-5-yl)-5-[N-(2,2,2-trifluoroacetyl)amino]phenyl}propionate(Intermediate 57)

A solution of Intermediate 56 (1.62 g) in a mixture of ethyl acetate (10ml) and methanol (3 ml) was added with 10% palladium/carbon (29 mg), andstirred at room temperature for 17 hours under hydrogen atmosphere. Thereaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure to obtain the title compound(Intermediate 57, 1.19 g).

Examples S-1 to S-73

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-S-1 and Table-S-2.

TABLE S-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass S-1 cPenO H NHMe 2-Nap S-1S-2 cPenO H NHEt 2-Nap S-1 S-3 cPenO Me NHAc 2-Nap S-3 S-4 cPenO H NHAc2-Nap S-4 C 421 (M⁺ + 1) S-5 cPenO H NHCHO 2-Nap S-5 C 407 (M⁺ + 1) S-6cPenO H NHCOCH₂OAc 2-Nap S-6 S-7 cPenO H NHCOCH₂OH 2-Nap S-7 C 437(M⁺ + 1) S-8 cPenO H NHCONH₂ 2-Nap S-8 C 422 (M⁺ + 1) S-9 cPenO MeNHSO₂Me 2-Nap S-9 S-10 cPenO H NHSO₂Me 2-Nap S-10 C 456 (M⁺) S-11 cPenOH NHSO₂NMe₂ 2-Nap S-11 C 483 (M⁺ + 1) S-12 cPenO H NMe₂ 2-Nap S-12 S-13cPenO H NHMe 1Me-5-Ind S-1 S-14 cPenO H NMe₂ 1Me-5-Ind S-12 C 407(M⁺ + 1) S-15 cPenO H NHMe 1Me-5-1HIdz S-1 C 394 (M⁺ + 1) S-16 cPenO HNMe₂ 1Me-5-1HIdz S-12 S-17 cPenO H NHMe 5-Bzt S-1 S-18 cPenO H NMe₂5-Bzt S-12 S-19 cPenO H NHMe 5-2ABzt S-1 S-20 cPenO H NMe₂ 5-2ABzt S-12S-21 cPenO H NHMe 2Me-5-Bzt S-1 S-22 cPenO H NMe₂ 2Me-5-Bzt S-12 S-23cPenMeO H NHMe 1Me-5-Ind S-1 S-24 cPenMeO H NMe₂ 1Me-5-Ind S-12 S-25cPenMeO H NHMe 1Me-5-1HIdz S-1 S-26 cPenMeO H NMe₂ 1Me-5-1HIdz S-12 S-27cHexO H NHMe 2-Nap S-1 S-28 cHexO H NMe₂ 2-Nap S-12 S-29 cHexO H NHMe1Me-5-Ind S-1 C 421 (M⁺ + 1) S-30 cHexO H NMe₂ 1Me-5-Ind S-12 S-31 cHexOH NHMe 1Me-5-1HIdz S-1 S-32 cHexO H NMe₂ 1Me-5-1HIdz S-12 S-33 2EtBuO HNHMe 2-Nap S-1 C 406 (M⁺ + 1) S-34 2EtBuO H NHMe 6-OMe-2-Nap S-1 S-352EtBuO H NHMe 1Me-5-Ind S-1 S-36 2EtBuO H NHMe 5-Bzt S-1 S-37 2EtBuO HNHMe 1Me-5-1HIdz S-1 S-38 iBuO H NHMe 2-Nap S-1 S-39 iBuO H NMe₂ 2-NapS-12 C 392 (M⁺ + 1) S-40 iBuO H NHMe 1Me-5-Ind S-1 C 381 (M⁺ + 1) S-41iBuO H NMe₂ 1Me-5-Ind S-12 S-42 iBuO H NHMe 1Me-5-1HIdz S-1 S-43 iBuO HNMe₂ 1Me-5-1HIdz S-12 S-44 1PhEtO H NHMe 2-Nap S-1 C 426 (M⁺ + 1) S-451PhEtO H NMe₂ 2-Nap S-12

TABLE S-2 S-46 1PhEtO H NHMe 1Me-5-Ind S-1 S-47 1PhEtO H NMe₂ 1Me-5-IndS-12 C 443 (M⁺ + 1) S-48 1PhEtO H NHMe 1Me-5-1HIdz S-1 C 429 (M⁺ + 1)S-49 1PhEtO H NMe₂ 1Me-5-1HIdz S-12 S-50 4CF₃BnO H NHMe 2-Nap S-1 S-514CF₃BnO H NMe₂ 2-Nap S-12 S-52 4CF₃BnO H NHMe 1Me-5-Ind S-1 S-53 4CF₃BnOH NMe₂ 1Me-5-Ind S-12 C 497 (M⁺ + 1) S-54 4CF₃BnO H NHMe 1Me-5-1HIdz S-1S-55 4CF₃BnO H NMe₂ 1Me-5-1HIdz S-12 S-56 2-IndanO H NHMe 2-Nap S-1 S-572-IndanO H NMe₂ 2-Nap S-12 S-58 2-IndanO H NHMe 1Me-5-Ind S-1 C 441(M⁺ + 1) S-59 2-IndanO H NMe₂ 1Me-5-Ind S-12 S-60 2-IndanO H NHMe1Me-5-1HIdz S-1 A 4.16 442 (M⁺ + 1) S-61 2-IndanO H NMe₂ 1Me-5-1HIdzS-12 A 4.18 456 (M⁺ + 1) S-62 2(4FPh)EtO H NHMe 2-Nap S-1 S-632(4FPh)EtO H NMe₂ 2-Nap S-12 C 458 (M⁺ + 1) S-64 2(4FPh)EtO H NHMe1Me-5-Ind S-1 C 447 (M⁺ + 1) S-65 2(4FPh)EtO H NMe₂ 1Me-5-Ind S-12 S-662(4FPh)EtO H NHMe 1Me-5-1HIdz S-1 S-67 2(4FPh)EtO H NMe₂ 1Me-5-1HIdzS-12 S-68 2(4DMAPh)EtO H NHMe 2-Nap S-1 C 469 (M⁺ + 1) S-69 2(4DMAPh)EtOH NMe₂ 2-Nap S-12 S-70 2(4DMAPh)EtO H NHMe 1Me-5-Ind S-1 S-712(4DMAPh)EtO H NMe₂ 1Me-5-Ind S-12 C 486 (M⁺ + 1) S-72 2(4DMAPh)EtO HNHMe 1Me-5-1HIdz S-1 C 473 (M⁺ + 1) S-73 2(4DMAPh)EtO H NMe₂ 1Me-5-1HIdzS-12

Example T-1 Synthesis of3-[4-cyclopentylmethyloxy-3-hydroxy-5-(naphthalen-2-yl)phenyl]propionicacid (Compound No. T-1)

A solution of Compound No. Q-2 (403 mg) in acetic acid (1.5 ml) wasadded with 20% sulfuric acid (1.0 ml). This reaction mixture was addeddropwise with an aqueous solution (0.5 ml) of sodium nitrite (76 mg)over 10 minutes while keeping the temperature of the reaction mixturebelow 10° C., and further stirred for 5 minutes. This reaction solutionwas added to a solution of sodium acetate (328 mg) in acetic acid (3.5ml) heated and stirred at 100° C. beforehand, and further stirred for 10minutes with heating. The reaction solution was poured into ice water(50 ml), and extracted with isopropyl ether (100 ml×2). The organiclayer was washed successively with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:ethyl acetate=10:1). The obtained substance was reacted with 2 Naqueous sodium hydroxide (500 μl) and treated according to the proceduredescribed in the synthesis method of Intermediate 9 to obtain the titlecompound (Compound No. T-1, 78 mg).

Example T-2 Synthesis of ethyl3-[3-acetoxy-4-cyclopentyloxy-5-(naphthalen-2-yl)phenyl]propionate(Intermediate 58)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 13hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=9:1), Compound No. B-114 (160 mg),2-naphthaleneboronic acid (382 mg, Ald), 2 M aqueous sodium carbonate(0.7 ml) and (Ph₃P)₄Pd (105 mg) were reacted and treated to obtain thetitle compound (Intermediate 58, 152 mg).

Synthesis of3-[4-cyclopentyloxy-3-hydroxy-5-(naphthalen-2-yl)phenyl]propionic acid(Compound No. T-2)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Intermediate 58 (146 mg) and 2 N aqueous sodium hydroxide (0.35 ml) werereacted and treated to obtain the title compound (Compound No. T-2, 135mg).

Example T-31 Synthesis of ethyl3-[4-cyclopentyloxy-3-methoxy-5-(naphthalen-2-yl)phenyl]propionate(Compound No. T-31)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 14hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=9:1), Compound No. A-25 (210 mg),2-naphthaleneboronic acid (184 mg), 2 M aqueous sodium carbonate (0.5ml) and (Ph₃P)₄Pd (65.3 mg) were reacted and treated to obtain the titlecompound (Compound No. T-31, 181 mg).

Example T-32 Synthesis of3-[4-cyclopentyloxy-3-methoxy-5-(naphthalen-2-yl)phenyl]propionic acid(Compound No. T-32)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. T-31 (166 mg) and 2 N aqueous sodium hydroxide (0.45 ml)were reacted and treated to obtain the title compound (Compound No.T-32, 135 mg).

Example T-33 Synthesis of4-(t-butyldimethylsilyloxy)-3-(1H-indol-5-yl)-5-methoxybenzaldehyde(Intermediate 59)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for12.5 hours, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=7:1), 5-indoleboronic acid (1.29g), Intermediate 16 (1.75 g), 2 M aqueous sodium carbonate (4.8 ml) and(Ph₃P)₄Pd (400 mg) were reacted and treated to obtain the title compound(Intermediate 59, 910 mg).

Synthesis of ethyl3-[4-(t-butyldimethylsilyloxy)-3-(1H-indol-5-yl)-5-methoxyphenyl]acrylate(Intermediate 60)

According to the procedure described in the synthesis method ofIntermediate 7 with the modifications that the reaction was carried outfor 1.5 hours, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=3:1), Intermediate 59 (910 mg),ethyl diethylphosphonoacetate (500 μl) and 60% sodium hydride (100 mg)were reacted and treated to obtain the title compound (Intermediate 60,945 mg).

Synthesis of ethyl3-[4-(t-butyldimethylsilyloxy)-3-(1H-indol-5-yl)-5-methoxyphenyl]propionate(Intermediate 61)

According to the procedure described in the synthesis method ofIntermediate 8, Intermediate 60 (945 mg) and 10% palladium/carbon (95mg) were reacted and treated under hydrogen gas atmosphere to obtain thetitle compound (Intermediate 61, 940 mg).

Synthesis of ethyl3-[4-hydroxy-3-(1H-indol-5-yl)-5-methoxyphenyl]propionate (Intermediate62)

According to the procedure described in the synthesis method ofIntermediate 19 with the modifications that the reaction was carried outfor 1.5 hours, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=2:1), Intermediate 61 (750 mg) anda 1 M solution of tetrabutylammonium fluoride in THF (5.0 ml) werereacted and treated to obtain the title compound (Intermediate 62, 555mg).

Synthesis of ethyl3-[4-cyclopentyloxy-3-(1H-indol-5-yl)-5-methoxyphenyl]propionate(Compound No. T-33)

According to the procedure described in the synthesis method of CompoundNo. A-6 with the modifications that the reaction was carried out for 16hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=7:1), Intermediate 62 (340 mg), Ph₃P (1.31g), cyclopentanol (450 μl) and TMAD (860 mg) were reacted and treated toobtain the title compound (Compound No. T-33, 376 mg).

Example T-34 Synthesis of3-[4-cyclopentyloxy-3-(1H-indol-5-yl)-5-methoxyphenyl]propionic acid(Compound No. T-34)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. T-33 (99 mg) and 2 N aqueous sodium hydroxide (500 μl) werereacted and treated to obtain the title compound (Compound No. T-34, 76mg).

Examples T-1 to T-61

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-T-1 and Table T-2.

TABLE T-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass T-1 cPenMeO H OH 2-Nap T-1 A5.03 382 (M⁺ + 1) T-2 cPenO H OH 2-Nap T-2 T-3 cPenO H OH 5-Ind Int73,T-2 C 366 (M⁺ + 1) T-4 cPenO H OH 1Me-5-Ind Int73, T-2 T-5 cPenO H OH5-1HIdz Int73, T-2 T-6 cPenO H OH 1Me-5-Idz Int73, T-2 C 381 (M⁺ + 1)T-7 cHexO H OH 2-Nap T-1 T-8 cHexO H OH 1Me-5-Ind T-1 T-9 cHexO H OH1Me-5-Idz T-1 T-10 2EtBuO H OH 2-Nap T-1 C 393 (M⁺ + 1) T-11 2EtBuO H OH1Me-5-Ind T-1 T-12 2EtBuO H OH 1Me-5-Idz T-1 T-13 iBuO H OH 2-Nap T-1T-14 iBuO H OH 1Me-5-Ind T-1 T-15 iBuO H OH 1Me-5-Idz T-1 T-16 1PhEtO HOH 2-Nap T-1 T-17 1PhEtO H OH 1Me-5-Ind T-1 C 416 (M⁺ + 1) T-18 1PhEtO HOH 1Me-5-Idz T-1 T-19 4CF₃BnO H OH 2-Nap T-1 T-20 4CF₃BnO H OH 1Me-5-IndT-1 T-21 4CF₃BnO H OH 1Me-5-Idz T-1 T-22 2-IndanO H OH 2-Nap T-1 T-232-IndanO H OH 1Me-5-Ind T-1 T-24 2-IndanO H OH 1Me-5-Idz T-1 A 3.91 429(M⁺ + 1) T-25 2(4FPh)EtO H OH 2-Nap T-1 T-26 2(4FPh)EtO H OH 1Me-5-IndT-1 T-27 2(4FPh)EtO H OH 1Me-5-Idz T-1 T-28 2(4DMAPh)EtO H OH 2-Nap T-1T-29 2(4DMAPh)EtO H OH 1Me-5-Ind T-1 C 459 (M⁺ + 1) T-30 2(4DMAPh)EtO HOH 1Me-5-Idz T-1 T-31 cPenO Et OMe 2-Nap T-31 T-32 cPenO H OMe 2-NapT-32 T-33 cPenO Et OMe 5-Ind T-33 T-34 cPenO H OMe 5-Ind T-34 T-35 cPenOH OMe 1Me-5-Ind T-33, T-34 A 4.72 394 (M⁺ + 1) T-36 cPenO H OMe 5-1HIdzT-31, T-32 T-37 cPenO H OMe 1Me-5-Idz T-31, T-32 T-38 cHexO H OMe 2-NapT-31, T-32 C 405 (M⁺ + 1) T-39 cHexO H OMe 1Me-5-Ind T-33, T-34 T-40cHexO H OMe 1Me-5-Idz T-31, T-32 T-41 2EtBuO H OMe 2-Nap T-31, T-32 T-422EtBuO H OMe 1Me-5-Ind T-33, T-34 T-43 2EtBuO H OMe 1Me-5-Idz T-31, T-32

TABLE T-2 T-44 iBuO H OMe 2-Nap T-31, T-32 T-45 iBuO H OMe 1Me-5-IndT-33, T-34 C 382 (M⁺ + 1) T-46 iBuO H OMe 1Me-5-1HIdz T-31, T-32 T-471PhEtO H OMe 2-Nap T-31, T-32 T-48 1PhEtO H OMe 1Me-5-Ind T-33, T-34T-49 1PhEtO H OMe 1Me-5-1HIdz T-31, T-32 C 431 (M⁺ + 1) T-50 4CF₃BnO HOMe 2-Nap T-31, T-32 T-51 4CF₃BnO H OMe 1Me-5-Ind T-33, T-34 T-524CF₃BnO H OMe 1Me-5-1HIdz T-31, T-32 T-53 2-IndanO H OMe 2-Nap T-31,T-32 T-54 2-IndanO H OMe 1Me-5-Ind T-33, T-34 T-55 2-IndanO H OMe1Me-5-1HIdz T-31, T-32 C 443 (M⁺ + 1) T-56 2(4FPh)EtO H OMe 2-Nap T-31,T-32 T-57 2(4FPh)EtO H OMe 1Me-5-Ind T-33, T-34 C 448 (M⁺ + 1) T-582(4FPh)EtO H OMe 1Me-5-1HIdz T-31, T-32 T-59 2(4DMAPh)EtO H OMe 2-NapT-31, T-32 C 470 (M⁺ + 1) T-60 2(4DMAPh)EtO H OMe 1Me-5-Ind T-33, T-34T-61 2(4DMAPh)EtO H OMe 1Me-5-1HIdz T-31, T-32

Example U-1 Synthesis of4-cyclohexylmethyloxy-3-(naphthalen-2-yl)phenylacetonitrile(Intermediate 63)

A solution of Compound No. C-1 (172 mg) in dehydrated THF (5 ml) wasadded successively with trimethylsilylnitrile (133 μl, TCI) under icecooling and zinc iodide (16 mg, WAKO) under argon gas atmosphere,stirred for 15 minutes, then warmed to room temperature, and furtherstirred for 27 hours. The reaction mixture was added with ethyl acetate(90 ml), and washed successively with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride and saturatedbrine. The organic layer was dried, and then the solvent was evaporatedunder reduced pressure. A solution of the residue in anhydrous methylenechloride (5 ml) was added with triethylsilane (240 μl, TCI) under icecooling and boron trifluoride diethyl ether complex (366 μl, TCI) underargon gas atmosphere, warmed to room temperature, and stirred for 3.5hours. The reaction mixture was poured into ice water (50 ml), andextracted with ethyl acetate (90 ml). The organic layer was successivelywashed with saturated aqueous sodium hydrogencarbonate, saturatedaqueous ammonium chloride, and saturated brine and dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=10:1) to obtain thetitle compound (Intermediate 63, 116 mg).

Synthesis of 4-cyclohexylmethyloxy-3-(naphthalen-2-yl)phenylacetic acid(Compound No. U-1)

According to the procedure described in the synthesis method ofIntermediate 9 with the modifications that the reaction was carried outfor 24 hours under reflux by heating, and the purification was performedby column chromatography (Quad, hexane:ethyl acetate=2:1), Intermediate63 (110 mg) and 5 N aqueous sodium hydroxide (900 μl) were reacted andtreated to obtain the title compound (Compound No. U-1, 62 mg).

Example U-10 Synthesis of methyl4-[4-cyclopentylmethyloxy-3-(naphthalen-2-yl)phenyl]butyrate (CompoundNo. U-10)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 18hours, and the purification was performed by column chromatography(Quad, hexane:isopropyl ether=8:1), Compound No. F-1 (355 mg),2-naphthaleneboronic acid (344 mg), 2 M aqueous sodium carbonate (2.1ml) and (Ph₃P)₄Pd (115 mg) were reacted and treated to obtain the titlecompound (Compound No. U-10, 392 mg).

Example U-11 Synthesis of4-[4-cyclopentylmethyloxy-3-(naphthalen-2-yl)phenyl]butyric acid(Compound No. U-11)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3.5 hours,Compound No. U-10 (380 mg) and 2 N aqueous sodium hydroxide (1.0 ml)were reacted and treated to obtain the title compound (Compound No.U-11, 342 mg).

Examples U-1 to U-18

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-U-1.

TABLE U-1

LCMS Exp. RxO Y Zx n AR Syn method RTime Mass U-1 cHexMeO H H 1 2-NapU-1 C 374 (M⁺) U-2 cHexMeO H H 1 1Me-5-Ind Int63, U-1 U-3 cHexMeO H H 11Me-5-Idz Int63, U-1 U-4 cPenMeO H H 1 2-Nap Int63, U-1 C 360 (M⁺) U-5cPenMeO H H 1 1Me-5-Ind Int63, U-1 U-6 cPenO H H 1 2-Nap Int63, U-1 U-7cPenO H H 1 1Me-5-Ind Int63, U-1 C 349 (M⁺) U-8 2(4FPh)EtO H H 1 2-NapInt63, U-1 U-9 2(4FPh)EtO H H 1 1Me-5-Ind Int63, U-1 U-10 cPenMeO Me H 32-Nap U-10 C 374 (M⁺) U-11 cPenMeO H H 3 2-Nap U-11 C 374 (M⁺) U-12cPenMeO H H 3 1Me-5-Ind U-10, U-11 U-13 cPenO H H 3 2-Nap U-10, U-11U-14 cPenO H H 3 1Me-5-Ind U-10, U-11 C 377 (M⁺) U-15 cHexO H H 3 2-NapU-10, U-11 U-16 cHexO H H 3 1Me-5-Ind U-10, U-11 U-17 2(4FPh)EtO H H 32-Nap U-10, U-11 U-18 2(4FPh)EtO H H 3 1Me-5-Ind U-10, U-11

Example V-1 Synthesis of ethyl3-[4-cyclohexylmethyloxy-3-(naphthalen-1-yl)phenyl]acrylate(Intermediate 64)

According to the procedure described in the synthesis method ofIntermediate 7 provided that the reaction was carried out for 1 hour,Compound No. C-2 (361 mg), ethyl diethylphosphonoacetate (240 μl), 60%sodium hydride (69 mg) were reacted and treated to obtain the titlecompound (Intermediate 64, 377 mg).

Synthesis of ethyl3-[4-cyclohexylmethyloxy-3-(naphthalen-1-yl)phenyl]propionate (CompoundNo. V-1)

According to the procedure described in the synthesis method ofIntermediate 8 with the modifications that the reaction was carried outfor 1.5 hours, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=10:1), Intermediate 64 (361 mg) and10% palladium/carbon (49 mg) were reacted under hydrogen atmosphere andtreated to obtain the title compound (Compound No. V-1, 344 mg).

Example V-2 Synthesis of3-[4-cyclohexylmethyloxy-3-(naphthalen-1-yl)phenyl]propionic acid(Compound No. V-2)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 1.5 hours,Compound No. V-1 (332 mg) and 2 N aqueous sodium hydroxide (900 μl) werereacted and treated to obtain the title compound (Compound No. V-2, 295mg).

Example V-3 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(6-hydroxynaphthalen-2-yl)phenyl]propionate(Compound No. V-3)

A solution of 2-bromo-6-hydroxynaphthalene (243 mg, TCI) in anhydrousTHF (10 ml) was cooled to −78° C., added dropwise with a 1.6 M solutionof n-butyllithium in hexane (1.18 ml) over 20 minutes under argon gasatmosphere, and stirred for 30 minutes. The reaction mixture was addeddropwise with (^(i)PrO)₃B (1.73 ml) over 10 minutes, stirred for 30minutes, then warmed to room temperature, and further stirred for 2hours. The reaction mixture was added with 0.5 M aqueous sulfuric acid(2 ml), and extracted with diethyl ether (40 ml×3). The organic layerwas washed with saturated brine and dried, and then the solvent wasevaporated under reduced pressure to obtain crude6-hydroxy-2-naphthaleneboronic acid (378 mg). A solution of thissubstance in ethanol (1 ml), Compound No. A-1 (230 mg), and 2 M aqueoussodium carbonate (2.4 ml) were added with toluene (3 ml) and (Ph₃P)₄Pd(115 mg) and stirred at 100° C. for 13 hours. The reaction mixture wasadded with ethyl acetate (100 ml), and washed successively withsaturated aqueous sodium hydrogencarbonate, saturated aqueous ammoniumchloride and saturated brine. The organic layer was dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby flash column chromatography (hexane:ethyl acetate=6:1) to obtain thetitle compound (Compound No. V-3, 270 mg).

Example V-4 Synthesis of3-[4-cyclopentylmethyloxy-3-(6-hydroxynaphthalen-2-yl)phenyl]propionicacid (Compound No. V-4)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 14 hours,Compound No. V-3 (149 mg) and 2 N aqueous sodium hydroxide (370 μl) werereacted and treated to obtain the title compound (Compound No. V-4, 117mg).

Example V-5 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(5-hydroxynaphthalen-2-yl)phenyl]propionate(Compound No. V-5)

2-Amino-5-hydroxynaphthalene (4.80 g, TCI) was dissolved in 6 Nhydrochloric acid (300 ml), added dropwise with an aqueous solution(22.5 ml) of sodium nitrite (2.25 g) over 30 minutes under ice cooling,and stirred for 30 minutes. The reaction mixture was added dropwise withan aqueous solution (75 ml) of potassium iodide (9.90 g, WAKO), stirredfor 30 minutes, then warmed to room temperature, and further stirred for3.5 hours. The reaction mixture was neutralized with aqueous ammonia,and then filtered through a Celite layer. The filtrate was added withethyl acetate (90 ml×2) for extraction. The organic layer was washedsuccessively with saturated aqueous sodium hydrogencarbonate, saturatedaqueous ammonium chloride and saturated brine, and dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=10:1) to obtain1-hydroxy-6-iodonaphthalene (1.48 g). A solution of this substance (539mg) in anhydrous THF (10 ml) was added with 60% sodium hydride (171 mg)under ice cooling, and stirred for 1 hour. The reaction mixture wascooled to −78° C. under argon gas atmosphere, added dropwise with a 1.6M solution of n-butyllithium in hexane (3.75 ml) over 10 minutes, andstirred for 30 minutes. The reaction mixture was added dropwise with(^(i)PrO)₃B (1.16 ml) over 10 minutes, stirred for 30 minutes, thenwarmed to room temperature, and further stirred for 3 hours. Thereaction mixture was added with water (3 ml) and 0.5 M aqueous sulfuricacid (7 ml), and extracted with diethyl ether (100 ml×3). The organiclayer was washed with saturated brine and dried, and then the solventwas evaporated under reduced pressure to obtain crude7-hydroxy-2-naphthaleneboronic acid. A solution of this substance inethanol (1 ml), Compound No. A-1 (350 mg), 2 M aqueous sodium carbonate(2.4 ml) and (Ph₃P)₄Pd (116 mg) were reacted and treated according tothe procedure described in the synthesis method of Compound No. V-3 withthe modifications that the reaction was carried out for 14 hours, andthe purification was performed by column chromatography (Quad,hexane:ethyl acetate=6:1) to obtain the title compound (Compound No.V-5, 388 mg).

Example V-6 Synthesis of3-[4-cyclopentylmethyloxy-3-(5-hydroxynaphthalen-2-yl)phenyl]propionicacid (Compound No. V-6)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 12 hours,Compound No. V-5 (355 mg) and 2 N aqueous sodium hydroxide (1.75 ml)were reacted and treated to obtain the title compound (Compound No. V-6,158 mg).

Example V-7 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(7-hydroxynaphthalen-2-yl)phenyl]propionate(Compound No. V-7)

According to the procedure described in the synthesis method of CompoundNo. V-5 with the modifications that the reaction was carried out for 4hours, and the purification was performed by flash column chromatography(hexane:ethyl acetate=6:1), crude 7-hydroxy-2-naphthaleneboronic acidprepared from 2-bromo-7-hydroxynaphthalene (559 mg, MAYB), a 1.6Msolution of n-butyllithium in hexane (3.91 ml) and (^(i)PrO)₃B (1.16ml), Compound No. A-1 (386 mg), 2 M aqueous sodium carbonate (4.0 ml)and (Ph₃P)₄Pd (195 mg) were reacted and treated to obtain the titlecompound (Compound No. V-7, 460 mg).

Example V-8 Synthesis of3-[4-cyclopentylmethyloxy-3-(7-hydroxynaphthalen-2-yl)phenyl]propionicacid (Compound No. V-8)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 27 hours,Compound No. V-7 (176 mg) and 2 N aqueous sodium hydroxide (436 μl) werereacted and treated to obtain the title compound (Compound No. V-8, 109mg).

Example V-11 Synthesis of methyl3-{4-cyclohexylmethyloxy-3-[6-(N,N-dimethylcarbamoylmethyloxy)naphthalen-2-yl]phenyl}propionate(Compound No. V-11)

A solution of Compound No. V-3 (185 mg) in DMF (5 ml) was added withpotassium carbonate (274 mg), and 2-chloro-N,N-dimethylacetamide (411μl, KANTO), and stirred at 50° C. for 18 hours. The reaction mixture wasadded with ethyl acetate (90 ml), and washed with saturated brine. Theorganic layer was dried, and then the solvent was evaporated underreduced pressure. The residue was purified by PTLC(chloroform:methanol=10:1) to obtain the title compound (Compound No.V-11, 213 mg).

Example V-12 Synthesis of3-{4-cyclohexylmethyloxy-3-[6-(N,N-dimethylcarbamoylmethyloxy)naphthalen-2-yl]phenyl}propionicacid (Compound No. V-10)

According to the procedure described in the synthesis method ofIntermediate 9 with the modifications that the reaction was carried outat room temperature for 18 hours and at 60° C. for 8 hours, and thepurification was performed by PTLC (chloroform:methanol=10:1), CompoundNo. V-11 (213 mg) and 2 N aqueous sodium hydroxide (420 μl) were reactedand treated to obtain the title compound (Compound No. V-12, 115 mg).

Example V-13 Synthesis of methyl3-[3-(6-aminonaphthalen-2-yl)-4-cyclopentylmethyloxyphenyl]propionate(Compound No. V-13)

According to a known method described in a publication (Anderson, L. C.et al., J. Am. Chem. Soc, 1943, vol. 65, p. 241), a solution of2-amino-6-bromonaphthalene (223 mg) obtainable from commerciallyavailable 2-bromo-6-hydroxynaphthalene (TCI) in anhydrous THF (10 ml)was added with 30% potassium hydride (191 mg, Ald) under ice cooling,and stirred for 1 hour. The reaction mixture was cooled to −78° C. underargon gas atmosphere, added dropwise with a 1.7 M solution oft-butyllithium in pentane (1.88 ml) over 10 minutes, and stirred for 30minutes. This reaction mixture was added dropwise with (^(i)PrO)₃B (0.92ml) over 10 minutes, stirred for 30 minutes, then warmed to roomtemperature, and further stirred for 3 hours. The reaction mixture wasadded with water (3 ml) and 0.5 M aqueous sulfuric acid (4 ml), andextracted with diethyl ether (100 ml×3). The organic layer was washedwith saturated brine and dried, and then the solvent was evaporatedunder reduced pressure to obtain crude 6-amino-2-naphthaleneboronic acid(402 mg). A solution of this substance in ethanol (0.5 ml), Compound No.A-1 (119 mg), 2 M aqueous sodium carbonate (1.5 ml) and (Ph₃P)₄Pd (61mg) were reacted and treated according to the procedure described in thesynthesis method of Compound No. V-3 with the modifications that thereaction was carried out for 13 hours, and the purification wasperformed by flash column chromatography (hexane:ethyl acetate=4:1) toobtain the title compound (Compound No. V-13, 129 mg).

Example V-14 Synthesis of3-[3-(6-aminonaphthalen-2-yl)-4-cyclopentylmethyloxyphenyl]propionicacid (Compound No. V-14)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 14 hours,Compound No. V-13 (120 mg) and 2 N aqueous sodium hydroxide (1.75 ml)were reacted and treated to obtain the title compound (Compound No.V-14, 89 mg).

Example V-16 Synthesis of methyl3-[3-({6-[2-(acetyloxy)acetylamino)naphthalen-2-yl}-4-cyclopentylmethyloxyphenyl)propionate(Intermediate 65)

A solution of Compound No. V-13 (151 mg) in dichloromethane (4 ml) wasadded with N-methylmorpholine (50 μl), and then added withacetyloxyacetyl chloride (48.3 μl) under ice cooling. The reactionmixture was stirred for 10 minutes, then warmed to room temperature, andfurther stirred for 4 hours. The reaction mixture was poured intoaqueous sodium hydrogencarbonate (100 ml), and ethyl acetate (150 ml)was added for extraction. The organic layer was successively washed withsaturated aqueous sodium hydrogencarbonate, saturated aqueous ammoniumchloride, and saturated brine and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by PTLC(hexane:ethyl acetate=1:1) to obtain the title compound (Intermediate88, 136 mg).

Synthesis of3-(4-cyclopentylmethyloxy-3-{6-[2-(hydroxyacetyl)amino]naphthalen-2-yl}phenyl)propionicacid (Compound No. V-16)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out at roomtemperature for 5 hours and at 60° C. for 1 hour, Intermediate 65 (135mg) and 2 N aqueous sodium hydroxide (1.12 ml) were reacted and treatedto obtain the title compound (Compound No. V-16, 102 mg).

Example V-18 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(6-methylsulfonylaminonaphthalen-2-yl)phenyl]propionate(Compound No. V-18)

A solution of Compound No. V-13 (149.1 mg) in 1,2-dichloroethane (5 ml)was added successively with pyridine (500 μl) and methanesulfonylchloride (62 μl) under ice cooling, stirred for 1.5 hours, then warmedto room temperature, and stirred for 12 hours. The reaction mixture wasadded with water (30 ml) and ethyl acetate (90 ml) for extraction. Theorganic layer was successively washed with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride, and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by PTLC (hexane:ethyl acetate=2:1) toobtain the title compound (Compound No. V-18, 126 mg).

Example V-19 Synthesis of3-[4-cyclopentylmethyloxy-3-(6-methylsulfonylaminonaphthalen-2-yl)phenyl]propionicacid (Compound No. V-19)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out at roomtemperature for 3 hours and at 60° C. for 1 hour, Compound No. V-18 (129mg) and 2 N aqueous sodium hydroxide (535 μl) were reacted and treatedto obtain the title compound (Compound No. V-19, 98 mg).

Example V-20 Synthesis of methyl3-{4-cyclopentylmethyloxy-3-[6-(N,N-dimethylsulfamoylamino)naphthalen-2-yl]phenyl}propionate(Compound No. V-20)

A solution of Compound No. V-13 (165 mg) in pyridine (5 ml) was addedsuccessively with 4-dimethylaminopyridine (104 mg, TCI) anddimethylsulfamoyl chloride (520 μl, TCI), stirred for 5 days, and thenfurther stirred at 50° C. for 4 hours. The reaction mixture was addedwith water (30 ml) and ethyl acetate (90 ml)) for extraction. Theorganic layer was washed with saturated brine and dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate 6:1) to obtain thetitle compound (Compound No. V-20, 125 mg).

Example V-21 Synthesis of3-{4-cyclopentylmethyloxy-3-[6-(N,N-dimethylsulfamoylamino)naphthalen-2-yl]phenyl}propionicacid (Compound No. V-21)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 1.5 hours,Compound No. V-20 (118 mg) and 2 N aqueous sodium hydroxide (460 μl)were reacted and treated to obtain the title compound (Compound No.V-21, 87 mg).

Example V-22 Synthesis of 2-bromo-6-sulfamoylaminonaphthalene(Intermediate 66)

A solution of chlorosulfonyl isocyanate (870 μl, WAKO) in benzene (10ml) was added dropwise with formic acid (377 μl, WAKO) under icecooling, warmed to room temperature, stirred and for 19.5 hours, thenwarmed to 40° C., and further stirred for 4 hours. The reaction mixturewas added dropwise with a solution of 2-amino-6-bromonaphthalene (443mg) in benzene (5 ml) under ice cooling, warmed to room temperature, andstirred 21.5 hours. The reaction mixture was filtered to obtain solid,and the solid was added with ethyl acetate, mixed and filtered again.The solvent of the filtrate was evaporated under reduced pressure. Theresidue was purified by column chromatography (Quad, hexane:ethylacetate=2:1) to obtain the title compound (Intermediate 66, 158 mg).

Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(6-sulfamoylaminonaphthalen-2-yl)phenyl]propionate(Compound No. V-22)

According to a procedure described in literature (Miyaura, N. et al.,Tetrahedron. Lett., 1997, p. 3447), Compound No. A-1 (209 mg),bis(pinacolate)diboron (177 mg, Ald),[1,1′-bis(diphenylphosphono)ferrocene]palladium(II) dichloride(hereinafter abbreviated as “PdCl₂(dppf)”, 28 mg, TCI) and potassiumacetate (182.3 mg, Ald) were added to DMF (6 ml), and heated to 80° C.with stirring under argon gas atmosphere for 5 hours. The reactionmixture was cooled to room temperature, then added with Intermediate 91(130 mg), PdCl₂(dppf) (30 mg) and 2 M aqueous sodium carbonate (0.9 ml),and heated to 80° C. for 21 hours with stirring under argon gasatmosphere. The reaction mixture was added with ethyl acetate (100 ml),washed with saturated brine and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=3:1) to obtain the titlecompound (Compound No. V-22, 46 mg).

Example V-23 Synthesis of3-[4-cyclopentylmethyloxy-3-(6-sulfamoylaminonaphthalen-2-yl)phenyl]propionicacid (Compound No. V-23)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 24 hours,Compound No. V-22 (41 mg) and 2 N aqueous sodium hydroxide (340 μl) werereacted and treated to obtain the title compound (Compound No. V-23, 22mg).

Example V-27 Synthesis of methyl3-[4-cyclopentyloxy-3-(1H-indol-5-yl)phenyl]propionate (Compound No.V-27)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out at 80°C. for 5 hours, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=5:1), Compound No. A-5 (367 mg),5-indoleboronic acid (310 mg, Frontier), 2 M aqueous sodium carbonate(0.9 ml) and (Ph₃P)₄Pd (132 mg) were reacted and treated to obtain thetitle compound (Compound No. V-27, 340 mg).

Example V-28 Synthesis of3-[4-cyclopentyloxy-3-(1H-indol-5-yl)phenyl]propionic acid (Compound No.V-28)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. V-27 (330 mg) and 2 N aqueous sodium hydroxide (1.40 ml)were reacted and treated to obtain the title compound (Compound No.V-28, 310 mg).

Example V-29 Synthesis of methyl3-[4-cyclopentyloxy-3-(1-methyl-1H-indol-5-yl)phenyl]propionate(Compound No. V-29)

A solution of Compound No. V-27 (123 mg) in DMF (5 ml) was added with60% sodium hydride (19 mg) under ice cooling, and stirred for 10minutes. The reaction mixture was added dropwise with methyl iodide (100μl), stirred for 10 minutes, then warmed to room temperature, andfurther stirred for 1 hour. The reaction mixture was poured into icewater, and ethyl acetate (100 ml) was added for extraction. The organiclayer was successively washed with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride, and saturatedbrine and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by flash column chromatography(hexane:ethyl acetate=8:1) to obtain the title compound (Compound No.V-29, 126 mg).

Example V-30 Synthesis of3-[4-cyclopentyloxy-3-(1-methyl-1H-indol-5-yl)phenyl]propionic acid(Compound No. V-30)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 1 hour,Compound No. V-29 (123 mg) and 2 N aqueous sodium hydroxide (330 μl)were reacted and treated to obtain the title compound (Compound No.V-30, 110 mg).

Example V-31 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(1H-indol-4-yl)phenyl]propionate (CompoundNo. V-31)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 21hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=6:1), Compound No. A-1 (200 mg),4-indoleboronic acid (170 mg) obtainable from 4-bromoindole (TCI)according to a known method described in a publication (Doll, M. et al.,J. Org. Chem., 1999, vol. 64, p. 1372), 2 M aqueous sodium carbonate(550 μl) and (Ph₃P)₄Pd (60 mg) were reacted and treated to obtain thetitle compound (Compound No. V-31, 214 mg).

Example V-32 Synthesis of3-[4-cyclopentylmethyloxy-3-(1H-indol-4-yl)phenyl]propionic acid(Compound No. V-32)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 1 hour,Compound No. V-31 (210 mg) and 2 N aqueous sodium hydroxide (0.60 ml)were reacted and treated to obtain the title compound (Compound No.V-32, 173 mg).

Example V-33 Synthesis of 4-bromo-1-methyl-1H-indole (Intermediate 67)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for 30minutes, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=10:1), 4-bromoindole (5 g), 60% sodiumhydride (1.14 g) and methyl iodide (3.18 ml, TCI) were reacted andtreated to obtain the title compound (Intermediate 67, 4.95 g).

Synthesis of 1-methyl-1H-indole-4-boronic acid (Intermediate 68)

A solution of Intermediate 67 (4.90 g) in anhydrous THF (30 ml) wascooled to −78° C. under argon gas atmosphere, then added dropwise with a1.62 M solution of t-butyllithium in pentane (28.8 ml) over 30 minutes,and stirred for 30 minutes. This reaction mixture was added dropwisewith (^(i)PrO)₃B (10.77 ml) over 10 minutes, stirred for 1 hour, thenwarmed to room temperature, and further stirred for 2.5 hours. Thereaction mixture was poured into 1.2 N aqueous phosphoric acid (250 ml)containing ice, and extracted with diethyl ether (200 ml×3). The organiclayer was extracted with 0.4 N aqueous sodium hydroxide (150 ml×3), andthe aqueous layer was made acidic with 5 N hydrochloric acid under icecooling, and extracted with diethyl ether (200 ml×3) again. The organiclayer was washed with saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was washed withhexane to obtain the title compound (Intermediate 68, 3.17 g).

Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(1-methyl-1H-indol-4-yl)phenyl]propionate(Compound No. V-33)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for 18hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=9:1), Compound No. A-1 (200 mg),Intermediate 68 (185 mg), 2 M aqueous sodium carbonate (550 μl) and(Ph₃P)₄Pd (60 mg) were reacted and treated to obtain the title compound(Compound No. V-33, 208 mg).

Example V-34 Synthesis of3-[4-cyclopentylmethyloxy-3-(1-methyl-1H-indol-4-yl)phenyl]propionicacid (Compound No. V-34)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. V-33 (200 mg) and 2 N aqueous sodium hydroxide (0.60 ml)were reacted and treated to obtain the title compound (Compound No.V-34, 182 mg).

Example V-43 Synthesis of3-{4-cyclopentylmethyloxy-3-[1-(2-hydroxyethyl)-1H-indol-5-yl]phenyl}propionicacid (Compound No. V-43)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for1.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=8:1), Compound No. V-27 (144 mg), 60% sodiumhydride (38 mg) and ethyl bromoacetate (160 μl, TCI) were reacted andtreated to obtain an oily substance. This substance was reacted with 2 Naqueous sodium hydroxide (300 μl) and treated according to the proceduredescribed in the synthesis method of Intermediate 9 provided that thereaction was carried out for 1 hour to obtain the title compound(Compound No. V-43, 36 mg).

Example V-44 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(3-formyl-1H-indol-5-yl)phenyl]propionate(Compound No. V-44)

A solution of Compound No. V-27 (75 mg) in DMF (6 ml) was added dropwisewith phosphoryl chloride (30 μl, TCI) under ice cooling, stirring for 1hour, then warmed to 35° C., and further stirred for 1 hour. Thereaction mixture was added with 1 N aqueous sodium hydroxide (3 ml)containing ice, and extracted with ethyl acetate (90 ml). The organiclayer was washed with saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:ethyl acetate=5:1) to obtain the titlecompound (Compound No. V-44, 86 mg).

Example V-45 Synthesis of3-[4-cyclopentylmethyloxy-3-(3-formyl-1H-indol-5-yl)phenyl]propionicacid (Compound No. V-45)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. V-44 (86 mg) and 2 N aqueous sodium hydroxide (110 μl) werereacted and treated to obtain the title compound (Compound No. V-45, 60mg).

Example V-47 Synthesis of methyl3-[3-(3-acetyl-1H-indol-5-yl)-4-cyclopentylmethyloxyphenyl]propionate(Compound No. V-47)

A solution of Compound No. V-27 (98 mg) in methylene chloride (2 ml) wasadded with aluminum chloride (81 mg, Ald) and acetyl chloride (60 μl),and stirred for 4 hours. The reaction mixture was added with 1 Nhydrochloric acid (2 ml), and extracted with methylene chloride (60 ml).The organic layer was washed with saturated brine and dried, and thenthe solvent was evaporated under reduced pressure. The residue waspurified by flash column chromatography (hexane:ethyl acetate=4:1) toobtain the title compound (Compound No. V-47, 47 mg).

Example V-48 Synthesis of3-[3-(3-acetyl-1H-indol-5-yl)-4-cyclopentylmethyloxyphenyl]propionicacid (Compound No. V-48)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 4 hours,Compound No. V-47 (45 mg) and 2 N aqueous sodium hydroxide (110 μl) werereacted and treated to obtain the title compound (Compound No. V-48, 44mg).

Example V-50 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(3-methyl-1H-indol-5-yl)phenyl]propionate(Compound No. V-50)

According to the procedure described in the synthesis method ofIntermediate 95 with the modifications that the reaction was carried outfor 13 hours, and the purification was performed by flash columnchromatography (hexane:ethyl acetate=4:1), 5-bromo-3-methylindole (1.63g) obtainable from 5-bromoindole (TCI) by a known method described in apublication (Wayland, E. N., J. Org. Chem, 1967, vol. 32, p. 828) wasreacted with 30% potassium hydride (1.08 g), a 1.7 M solution oft-butyllithium in pentane (9.7 ml) and (^(i)PrO)₃B (3.75 ml) and treatedto obtain crude 3-methyl-5-indoleboronic acid. This compound was reactedwith Compound No. A-1 (803 mg), 2 M aqueous sodium carbonate (2 ml) and(Ph₃P)₄Pd (241 mg) and treated to obtain the title compound (CompoundNo. V-50, 552 mg).

Example V-51 Synthesis of3-[4-cyclopentylmethyloxy-3-(3-methyl-1H-indol-5-yl)phenyl]propionicacid (Compound No. V-51)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. V-50 (130 mg) and 2 N aqueous sodium hydroxide (370 μl)were reacted and treated to obtain the title compound (Compound No.V-51, 127 mg).

Example V-54 Synthesis of 4-bromo-1H-indazole (Intermediate 69)

According to a known method described in a publication (Schumann, P. etal., Bioorg. Med. Chem. Lett., 2001, vol. 11, p. 1153), the titlecompound (Intermediate 69, 1.68 g) was obtained from commerciallyavailable 3-bromotoluidine (4.51 g, Ald).

Synthesis of methyl3-[4-cyclopentyloxy-3-(1H-indazol-4-yl)phenyl]propionate (Compound No.V-54)

According to the procedure described in the synthesis method of CompoundNo. V-22 provided that the purification was performed by flash columnchromatography (hexane:ethyl acetate=2:1), Compound No. A-5 (328 mg),bis(pinacolate)diboron (281 mg), PdCl₂(dppf) (61 mg) and potassiumacetate (303 mg) were reacted at 80° C. for 4 hours, and then thisreaction mixture was added with Intermediate 105 (161 mg), PdCl₂(dppf)(64 mg) and 2 M aqueous sodium carbonate (1.5 ml), reacted at 80° C. for9 hours and treated to obtain the title compound (Compound No. V-54, 111mg).

Example V-55 Synthesis of3-[4-cyclopentyloxy-3-(1H-indazol-4-yl)phenyl]propionic acid (CompoundNo. V-55)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. V-54 (108 mg) and 2 N aqueous sodium hydroxide (400 μl)were reacted and treated to obtain the title compound (Compound No.V-55, 99 mg).

Example V-57 Synthesis of4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-methylnitrobenzene(Intermediate 70)

According to the procedure described in the synthesis method of CompoundNo. V-22,5-bromo-2-nitrotoluene (4.30 g) synthesized by nitrating3-bromotoluene (WAKO) by a known method, bis(pinacolate)diboron (5.59g), PdCl₂(dppf) (440 mg) and potassium acetate (6.09 g) were heated withstirring at 80° C. for 3 hours under argon gas atmosphere. The reactionmixture was added with ethyl acetate (300 ml), and washed successivelywith saturated aqueous sodium hydrogencarbonate, saturated aqueousammonium chloride and saturated brine. The organic layer was dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by flash column chromatography (hexane:ethyl acetate=8:1) toobtain the title compound (Intermediate 70, 4.21 g).

Synthesis of4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-methylaniline(Intermediate 71)

According to the procedure described in the synthesis method of CompoundNo. Q-2 with the modification that the reaction was carried out for 30minutes, Intermediate 70 (4.20 g) and platinum oxide (50 mg) were added,then reacted and treated under hydrogen atmosphere to obtain the titlecompound (Intermediate 71, 2.81 g).

Synthesis of methyl3-(4′-amino-6-cyclopentyloxy-3′-methylbiphenyl-3-yl)propionate(Intermediate 72)

According to the procedure described in the synthesis method of CompoundNo. C-1 with the modifications that the reaction was carried out for15.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=6:1), Compound No. A-5 (701 mg),Intermediate 71 (604 mg), 2 M aqueous sodium carbonate (1.8 ml), and(Ph₃P)₄Pd (182 mg) were reacted and treated to obtain the title compound(Intermediate 72, 762 mg).

Synthesis of methyl3-[4-cyclopentyloxy-3-(1H-indazol-5-yl)phenyl]propionate (Compound No.V-57)

A solution of Intermediate 72 (760 mg) in acetic acid (4 ml) was addedwith an aqueous solution (0.7 ml) of sodium nitrite (156 mg) under icecooling, and stirred for 30 minutes. This reaction mixture was addedwith urea (350 mg), warmed to room temperature, stirred for 30 minutes,then added with toluene (8 ml) and water (4 ml), and further stirred for60 hours. The reaction mixture was extracted with toluene (50 ml×2). Theorganic layer was washed successively with saturated aqueous sodiumhydrogencarbonate, and saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was purified bycolumn chromatography (Quad, hexane:ethyl acetate=6:1) to obtain thetitle compound (Compound No. V-57, 411 mg).

Example V-58 Synthesis of3-[4-cyclopentyloxy-3-(1H-indazol-5-yl)phenyl]propionic acid (CompoundNo. V-58)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2.5 hours,Compound No. V-57 (86 mg) and 2 N aqueous sodium hydroxide (250 μl) werereacted and treated to obtain the title compound (Compound No. V-58, 82mg).

Example V-66 Synthesis of 5-bromo-3-methyl-1H-indazole (Intermediate 73)

According to the procedure described in the synthesis method of CompoundNo. V-57 provided that the reaction was carried out for 121 hours,4-bromo-2-ethylaniline (5.01 g, LANC) and sodium nitrite (1.918 g) werereacted and treated to obtain the title compound (Intermediate 73, 3.30g).

Synthesis of methyl3-[4-cyclopentyloxy-3-(3-methyl-1H-indazol-5-yl)phenyl]propionate(Compound No. V-66)

According to the procedure described in the synthesis method of CompoundNo. V-22 provided that the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=5:2), Compound No. A-5 (434mg), bis(pinacolate)diboron (367 mg), PdCl₂(dppf) (101 mg), andpotassium acetate (339 mg) were reacted at 80° C. for 4 hours, and thenthis reaction mixture was added with Intermediate 108 (273 mg),PdCl₂(dppf) (104 mg) and 2 M aqueous sodium carbonate (1.1 ml), reactedat 80° C. for 18 hours and treated to obtain the title compound(Compound No. V-66, 98 mg).

Example V-67 Synthesis of3-[4-cyclopentyloxy-3-(3-methyl-1H-indazol-5-yl)phenyl]propionic acid(Compound No. V-67)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. V-66 (97 mg) and 2 N aqueous sodium hydroxide (400 μl) werereacted and treated to obtain the title compound (Compound No. V-67, 54mg).

Example V-68 Synthesis of methyl3-[4-cyclopentyloxy-3-(1,3-dimethyl-1H-indazol-5-yl)phenyl]propionate(Compound No. V-68)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for 16hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=3:1), Compound No. V-66 (112 mg), 60% sodiumhydride (24 mg) and methyl iodide (95 μl) were reacted and treated toobtain the title compound (Intermediate 110, 45 mg).

Example V-69 Synthesis of3-[4-cyclopentyloxy-3-(1,3-dimethyl-1H-indazol-5-yl)phenyl]propionicacid (Compound No. V-69)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. V-68 (45 mg) and 2 N aqueous sodium hydroxide (120 μl) werereacted and treated to obtain the title compound (Compound No. V-69, 42mg).

Example V-73 Synthesis of methyl3-[3-(benzo[b]thiophen-5-yl)-4-cyclopentylmethyloxyphenyl]propionate(Compound No. V-73)

According to the procedure described in the synthesis method of CompoundNo. V-22 provided that the purification was performed by columnchromatography (Quad, hexane ethyl acetate=10:1), Compound No. A-1 (371mg), bis(pinacolate)diboron (294 mg), PdCl₂(dppf) (67 mg) and potassiumacetate (308 mg) were reacted at 80° C. for 10 hours, and then thisreaction mixture was added with 5-bromobenzo[b]thiophene (301.4 mg)obtainable from 4-bromothiophenol (TCI) by a known method described in apublication (Seed, A. J., J. Mater. Chem., 2000, vol. 10, p. 2069),PdCl₂(dppf) (65 mg) and 2 M aqueous sodium carbonate (0.9 ml), reactedat 80° C. for 16 hours and treated to obtain the title compound(Compound No. V-73, 97 mg).

Example V-74 Synthesis of3-[3-(benzo[b]thiophen-5-yl)-4-cyclopentylmethyloxyphenyl]propionic acid(Compound No. V-74)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. V-73 (95 mg) and 2 N aqueous sodium hydroxide (250 μl) werereacted and treated to obtain the title compound (Compound No. V-74, 93mg).

Example V-77 Synthesis of (3-bromophenyl)thiourea (Intermediate 74)

A solution of 3-bromoaniline (10.89 ml, TCI) in 20% aqueous hydrochloricacid (18.2 ml) was added with ammonium thiocyanate (8.02 g, WAKO) andsodium hydrogensulfite (701 mg, WAKO), and stirred at 100° C. for 22hours. The reaction mixture was added with chloroform (20 ml) forextraction, and the organic layer was dried. Then, the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=2:1) to obtain the titlecompound (Intermediate 74, 4.45 g).

Synthesis of 2-amino-5-bromobenzothiazole (Intermediate 75)

A solution of Intermediate 74 (1.29 g) in chloroform (12 ml) was addeddropwise with a solution of bromine (272 μl, WAKO) in chloroform (1.5ml), refluxed by heating for 2.5 hours, and stirred at room temperaturefor 16 hours. The reaction mixture was concentrated under reducedpressure, neutralized with 5% aqueous ammonia, and then added with water(50 ml) and methylene chloride (150 ml) for extraction. The organiclayer was dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate 75,609 mg).

Synthesis of methyl3-[3-(2-aminobenzothiazol-5-yl)-4-cyclopentylmethyloxyphenyl]propionate(Compound No. V-77)

A solution of Intermediate 75 (459.1 mg) in anhydrous THF (30 ml) wasadded with N,N,N′,N′-tetramethylethylenediamine (1.51 ml, WAKO), cooledto −78° C. under argon gas atmosphere, then added dropwise with a 1.62 Msolution of t-butyllithium in pentane (7.06 ml), and stirred for 30minutes. The reaction mixture was added dropwise with (^(i)PrO)₃B (2.77ml), stirred for 30 minutes, then warmed to room temperature, andfurther stirred for 1.5 hours. The reaction mixture was added with 0.5 Maqueous sulfuric acid (7.5 ml) and extracted with diethyl ether (50ml×3). The organic layer was washed with saturated brine and dried, andthen the solvent was evaporated under reduced pressure to obtain crude2-amino-5-benzothiazoleboronic acid. This compound was reacted withCompound No. A-1 (344 mg), 2 M aqueous sodium carbonate (4.5 ml) and(Ph₃P)₄Pd (179 mg) and treated according to the procedure described inthe synthesis method of Compound No. V-3 with the modifications that thereaction was carried out for 12 hours, and the purification wasperformed by flash column chromatography (hexane:ethyl acetate=2:1) toobtain the title compound (Compound No. V-77, 76 mg).

Example V-78 Synthesis of3-[3-(2-aminobenzothiazol-5-yl)-4-cyclopentylmethyloxyphenyl]propionicacid (Compound No. V-78)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2.5 hours,Compound No. V-77 (77 mg) and 2 N aqueous sodium hydroxide (380 μl) werereacted and treated to obtain the title compound (Compound No. V-78, 69mg).

Example V-79 Synthesis of ethyl3-[3-(benzothiazol-5-yl)-4-cyclopentylmethyloxyphenyl]propionate(Compound No. V-79)

A solution of Compound No. V-77 (215 mg) in acetonitrile (10 ml) wasadded with 30% aqueous hypophosphorous acid (3 ml, WAKO), cooled to 0°C., added dropwise with an aqueous solution (1 ml) of sodium nitrite(187 mg), stirred for 30 minutes, then warmed to room temperature, andfurther stirred for 20 hours. The reaction mixture was poured into water(50 ml), neutralized by addition of 2 N aqueous sodium hydroxide, andadded with ethyl acetate (90 ml×3) for extraction. The organic layer waswashed with saturated brine and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate 10:1) to obtain the titlecompound (Compound No. V-79, 78 mg).

Example V-80 Synthesis of3-[3-(benzothiazol-5-yl)-4-cyclopentylmethyloxyphenyl]propionic acid(Compound No. V-80)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours,Compound No. V-79 (75 mg) and 2 N aqueous sodium hydroxide (500 μl) werereacted and treated to obtain the title compound (Compound No. V-80, 66mg).

Example V-81 Synthesis of methyl3-[4-cyclopentylmethyloxy-3-(2-methylbenzothiazol-5-yl)phenyl]propionate(Compound No. V-81)

According to the procedure described in the synthesis method of CompoundNo. V-13 with the modifications that the reaction was carried out for 13hours, and the purification was performed by flash column chromatography(hexane:ethyl acetate=5:1), crude 2-methyl-5-benzothiazoleboronic acidprepared from 5-bromo-2-methylbenzothiazole (684 mg, TCI), a 1.7 Msolution of t-butyllithium in pentane (7.06 ml) and (^(i)PrO)₃B (3.46ml), Compound No. A-1 (515 mg), 2 M aqueous sodium carbonate (6.5 ml)and (Ph₃P)₄Pd (258 mg) were reacted and treated to obtain the titlecompound (Compound No. V-81, 240 mg).

Example V-82 Synthesis of3-[4-cyclopentylmethyloxy-3-(2-methylbenzothiazol-5-yl)phenyl]propionicacid (Compound No. V-82)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 4 hours,Compound No. V-81 (227 mg) and 2 N aqueous sodium hydroxide (1.11 ml)were reacted and treated to obtain the title compound (Compound No.V-82, 132 mg).

Example V-83 Synthesis of ethyl3-{4-cyclopentylmethyloxy-3-[2-(N,N-dimethylamino)benzothiazol-6-yl]phenyl}propionate(Compound No. V-83)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for 4hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=7:1), Compound No. V-77 (155 mg), 60% sodiumhydride (16 mg) and methyl iodide (68.5 μl) were reacted and treated toobtain the title compound (Compound No. V-83, 48 mg).

Example V-84 Synthesis of3-{4-cyclopentylmethyloxy-3-[2-(N,N-dimethylamino)benzothiazol-6-yl]phenyl}propionicacid (Compound No. V-84)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 3 hours,Compound No. V-83 (47 mg) and 2 N aqueous sodium hydroxide (200 μl) werereacted and treated to obtain the title compound (Compound No. V-84, 35mg).

Example V-88 Synthesis of ethyl3-[3-(2-bromobenzothiazol-6-yl)-4-cyclohexylmethyloxyphenyl]propionate(Intermediate 76)

A solution obtained beforehand by adding t-butyl nitrite (178 μl, TCI)and copper(I) bromide (241 mg, WAKO) to acetonitrile (10 ml) and mixingthem was added dropwise with a solution of Compound No. V-83 (381 mg) inacetonitrile (5 ml) and stirred at room temperature for 1.5 hours. Thesolvent of the reaction mixture was concentrated under reduced pressure,and the residue was purified by column chromatography (Quad,hexane:ethyl acetate=10:1) to obtain the title compound (Intermediate76, 341 mg).

Synthesis of3-[4-cyclopentylmethyloxy-3-(2-methoxybenzothiazol-6-yl)phenyl]propionicacid (Compound No. V-88)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 18 hours,Intermediate 76 (169 mg) and 2 N aqueous sodium hydroxide (500 μl) werereacted and treated to obtain the title compound (Compound No. V-88, 114mg).

Example V-89 Synthesis of3-[4-cyclopentylmethyloxy-3-(2-oxo-2,3-dihydrobenzothiazol-6-yl)phenyl]propionicacid (Compound No. V-64)

A solution of Intermediate 76 (202 mg) in ethanol (8 ml) was added with5 N aqueous hydrochloric acid (1.5 ml), and stirred at 80° C. for 18.5hours. The reaction mixture was concentrated under reduced pressure, andadded with water (20 ml) and ethyl acetate (80 ml) for extraction. Theorganic layer was washed with saturated brine and dried, and then thesolvent was evaporated under reduced pressure. The residue was addedwith 2 N aqueous sodium hydroxide (1.0 ml), reacted and treatedaccording to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2 hours toobtain the title compound (Compound No. V-89, 250 mg).

Example V-91 Synthesis of3-[4-cyclopentylmethyloxy-3-(2-thioxo-2,3-dihydrobenzothiazol-6-yl)phenyl]propionicacid (Compound No. V-91)

A solution obtained beforehand by adding thiourea (52 mg, WAKO) to 1 Msulfuric acid (5 ml) and mixing them was added with a solution ofIntermediate 76 (101 mg) in acetonitrile (5 ml), and stirred at 90° C.for 20 hours. The reaction mixture was poured into water (20 ml),neutralized by addition of 1 N aqueous sodium hydroxide under icecooling, and then extracted with ethyl acetate (80 ml×3). The organiclayer was washed with saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was purified bycolumn chromatography (Quad, methylene chloride:ethanol=30:1) to obtainthe title compound (Compound No. V-91, 46 mg).

Synthesis examples for compounds used for preparation of the compoundsmentioned in the examples are shown below.

Syntheses of 4-bromo-1-methyl-1H-indazole (Intermediate 77) and4-bromo-2-methyl-2H-indazole (Intermediate 78)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for 8hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), Intermediate 69 (600 mg), 60% sodiumhydride (191 mg), and methyl iodide (379 μl) were reacted and treated toobtain the title compounds (Intermediate 119, 432 mg and Intermediate120, 164 mg).

Synthesis of 5-bromo-1H-indazole (Intermediate 79)

The title compound (Intermediate 121, 0.91 g) was obtained fromcommercially available 4-bromotoluidine (3.33 g, Ald) by a method knownfrom the aforementioned literature (Bioorg. Med. Chem. Lett., 2001, vol.11, p. 1153).

Syntheses of 5-bromo-1-methyl-1H-indazole (Intermediate 80) and5-bromo-2-methyl-2H-indazole (Intermediate 81)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for4.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), Intermediate 79 (300 mg), 60% sodiumhydride (80 mg), and methyl iodide (161 μl) were reacted and treated toobtain the title compounds (Intermediate 80, 201 mg and Intermediate 81,87 mg).

Synthesis of 1-methyl-1H-indazole-5-boronic acid (Intermediate 82)

According to the procedure described in the synthesis method of CompoundNo. V-3, Intermediate 80 (1.69 g), a 1.6 M solution of n-butyllithium inhexane (7.50 ml) and (^(i)PrO)₃B (3.23 ml) were reacted and treated toobtain the title compound (Intermediate 82, 1.39 g).

Syntheses of 5-bromo-1-ethyl-1H-indazole (Intermediate 83) and5-bromo-2-ethyl-2H-indazole (Intermediate 84)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for 2hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), Intermediate 79 (420 mg), 60% sodiumhydride (111 mg), and ethyl iodide (375 μl) were reacted and treated toobtain the title compounds (Intermediate 83, 250 mg and Intermediate 84,127 mg).

Synthesis of 6-bromo-1H-indazole (Intermediate 85)

The title compound was obtained from commercially available5-bromotoluidine (3.33 g, Ald) by the method known from theaforementioned literature (Bioorg. Med. Chem. Lett., 2001, vol. 11, p.1153) to obtain the title compound (Intermediate 85, 0.42 g).

Syntheses of 6-bromo-1-methyl-1H-indazole (Intermediate 86) and6-bromo-2-methyl-2H-indazole (Intermediate 87)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for2.5 hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=5:1), Intermediate 85 (277 mg), 60% sodiumhydride (86 mg), and methyl iodide (175 μl) were reacted and treated toobtain the title compounds (Intermediate 86, 196 mg and Intermediate 87,89 mg).

Synthesis of 5-bromo-2-t-butylthiobenzaldehyde (Intermediate 88)

A solution of 5-bromo-2-fluorobenzaldehyde (4.06 g, Avocado) in2-propanol (20 ml) was added with 2-methyl-2-propanethiol (2.26 ml, Ald)and potassium carbonate (3.04 g), and heated with stirring for 18 hours.The reaction mixture was cooled to room temperature, then poured intowater (50 ml), and extracted with chloroform (75 ml×3). The organiclayer was washed twice with saturated brine and dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby flash column chromatography (hexane:ethyl acetate=20:1) to obtain thetitle compound (Intermediate 88, 754 mg).

Synthesis of 5-bromobenzo[d]isothiazole (Intermediate 89)

A solution obtained beforehand by mixing 2 N aqueous sodium hydroxide(2.19 ml) in an aqueous solution (5 ml) of hydroxylamine hydrochloride(308 mg, WAKO) was added dropwise to a solution of Intermediate 88 (401mg) in ethanol (5 ml) at room temperature over 15 minutes. The reactionmixture was refluxed by heating for further 2 hours, then cooled to roomtemperature, poured into water (30 ml), and extracted with ethyl acetate(100 ml×3). The organic layer was washed successively with aqueoussaturated ammonium chloride aqueous, saturated aqueous sodiumhydrogencarbonate, and saturated brine and dried, and then the solventwas evaporated under reduced pressure. The residue was added withpolyphosphoric acid (21.4 g), and heated with stirring at 100° C. for 2hours. The reaction mixture was poured into ice water (100 ml),neutralized with 5 N aqueous sodium hydroxide under ice cooling, andthen extracted with ethyl acetate (100 ml×3). The organic layer waswashed twice with saturated brine and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:ethyl acetate=20:1) to obtain the titlecompound (Intermediate 89, 143 mg).

Synthesis of 5-bromobenzo[c]isothiazole (Intermediate 90)

A solution of methanesulfonamide (5.34 g, TCI) in dehydrated benzene (9ml) was added with thionyl chloride (6.0 ml) under ice cooling, andrefluxed by heating for 24 hours. The reaction mixture was concentratedunder reduced pressure, and a solution of the residue in dehydratedbenzene (4 ml) was added dropwise to a solution of 4-bromotoluidine(1.49 g) in dehydrated benzene (40 ml) under ice cooling. This mixturewas added dropwise with a solution of pyridine (0.97 ml) in dehydratedbenzene (4 ml) under ice cooling, and refluxed by heating for 80 hoursunder argon gas atmosphere. The reaction mixture was cooled to roomtemperature, poured into water (100 ml), and extracted with chloroform(100 ml×3). The organic layer was dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:ethyl acetate=10:1) to obtain the titlecompound (Intermediate 90, 618 mg).

Synthesis of 6-bromoimidazo[1,2-a]pyridine (Intermediate 91)

The title compound (Intermediate 91, 3.36 g) was obtained fromcommercially available bromoacetaldehyde-diethylacetal (4.7 ml, WAKO)and 2-amino-5-bromopyridine (4.32 g, Ald) by a known method described ina publication (Yamanaka, M. et al., Chem. Pharm. Bull., 1991, vol. 39,p. 1556).

Synthesis of 5-bromo-1H-pyrrolo[2,3-b]pyridine (Intermediate 92)

The title compound (Intermediate 92, 182 mg) was obtained fromcommercially available 1H-pyrrolo[2,3-b]pyridine (1.3 g, TCI) by a knownmethod described in a publication (Mazeas, D. et al, Heterocycles, 1999,vol. 50, p. 1065).

Synthesis of 5-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine (Intermediate93)

According to the procedure described in the synthesis method of CompoundNo. V-29 with the modifications that the reaction was carried out for 2hours, and the purification was performed by column chromatography(Quad, hexane:ethyl acetate=15:1), Intermediate 92 (98 mg), 60% sodiumhydride (33 mg), and methyl iodide (53 μl) were reacted and treated toobtain the title compound (Intermediate 93, 88 mg).

Synthesis of 6-bromoisoquinoline (Intermediate 94)

The title compound (Intermediate 94, 1.46 g) was obtained fromcommercially available 4-bromobenzaldehyde (15.0 g, WAKO) by a knownmethod described in a publication (Nerenz, H. et al., J. Chem. Soc.Perkin Trans. 2, 1998, p. 437].

Synthesis of 6-bromo-2H-isoquinolin-1-one (Intermediate 95)

A solution of Intermediate 94 (1.04 g) in methylene chloride (3 ml) wasadded with a solution of 3-chloroperbenzoic acid (2.16 g) in methylenechloride (3 ml), and stirred for 20 hours. The reaction mixture wasadded with methylene chloride (200 ml), and washed successively withsaturated aqueous sodium hydrogencarbonate, saturated aqueous ammoniumchloride and saturated brine. The organic layer was dried, and then thesolvent was evaporated under reduced pressure. A solution of the residuein acetic anhydride (10 ml) was refluxed by heating for 5 hours. Thereaction mixture was concentrated under reduced pressure, and then theresidue was added with 2.5 N aqueous sodium hydroxide (20 ml), andstirred at 100° C. for 1 hour. The reaction mixture was cooled to roomtemperature, and neutralized with 5 N aqueous hydrochloric acid underice cooling to obtain the precipitated title compound (Intermediate 95,623 mg).

Examples V-1 to V-115

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-V-1 to Table-V-3.

TABLE V-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass V-1 cHexMeO Et H 1-Nap V-1V-2 cHexMeO H H 1-Nap V-2 C 375 (M⁺ + 1) V-3 cPenMeO Me H 6OH-2-Nap V-3V-4 cPenMeO H H 6OH-2-Nap V-4 V-5 cPenMeO Me H 5OH-2-Nap V-5 V-6 cPenMeOH H 5OH-2-Nap V-6 V-7 cPenMeO Me H 7OH-2-Nap V-7 V-8 cPenMeO H H7OH-2-Nap V-8 V-9 cPenMeO Me H 6OMe-2-Nap V-1 V-10 cPenMeO H H6OMe-2-Nap V-2 C 418 (M⁺) V-11 cPenMeO Me H 6(OCH₂CONMe₂)-2-Nap V-11V-12 cPenMeO H H 6(OCH₂CONMe₂)-2-Nap V-12 V-13 cPenMeO Me H 6NH₂-2-NapV-13 V-14 cPenMeO H H 6NH₂-2-Nap V-14 V-15 cPenMeO H H 6(NMe₂)-2-NapV-13, V-14 C 418 (M⁺ + 1) V-16 cPenMeO H H 6(NHCOCH₂OH)-2-Nap V-16 V-17cPenMeO H H 6(NHCO-2-Furan)-2-Nap V-16 C 484 (M⁺ + 1) V-18 cPenMeO Me H6(NHSO₂Me)-2-Nap V-18 V-19 cPenMeO H H 6(NHSO₂Me)-2-Nap V-19 V-20cPenMeO Me H 6(NHSO₂NMe₂)-2-Nap V-20 V-21 cPenMeO H H 6(NHSO₂NMe₂)-2-NapV-21 V-22 cPenMeO Me H 6(NHSO₂NH₂)-2-Nap V-22 V-23 cPenMeO H H6(NHSO₂NH₂)-2-Nap V-23 V-24 cPenMeO H H 6(SO₂Me)-2-Nap V-22, V-23 C 452(M⁺) V-25 cPenMeO H H 6(SO₂NH₂)-2-Nap V-22, V-23 C 453 (M⁺) V-26 cPenMeOH H 6(SO₂NHMe)-2-Nap V-22, V-23 C 468 (M⁺ + 1) V-27 cPenO Me H 5-IndV-27 V-28 cPenO H H 5-Ind V-28 V-29 cPenO Me H 1Me-5-Ind V-29 V-30 cPenOH H 1Me-5-Ind V-30 V-31 cPenMeO Me H 4-Ind V-31 V-32 cPenMeO H H 4-IndV-32 V-33 cPenMeO Me H 1Me-4-Ind V-33 V-34 cPenMeO H H 1Me-4-Ind V-34V-35 cPenMeO H H 6-Ind V-31, V-32 C 377 (M⁺) V-36 cPenMeO H H 1Me-6-IndV-33, V-34 V-37 cPenMeO H H 2-Ind V-31, V-32 A 5.35 364 (M⁺ + 1) V-38cPenMeO H H 1Me-2-Ind V-29, V-30 V-39 cPenMeO H H 3-Ind V-31, V-32 V-40cPenMeO H H 1Me-3-Ind V-29, V-30 A 4.75 363 (M⁺ + 1) V-41 cPenMeO H H1iPr-5-Ind V-29, V-30 C 405 (M⁺) V-42 cPenMeO H H 1cPen-5-Ind V-29, V-30C 431 (M⁺) V-43 cPenMeO H H 1-(2OHEt)-5-Ind V-43

TABLE-V-2 V-44 cPenMeO Me H 3CHO-5-Ind V-44 V-45 cPenMeO H H 3CHO-5-IndV-45 V-46 cPenMeO H H 3CHO, 1Me-5-Ind V-29, V-30 C 406(M⁺ + 1) V-47cPenMeO Me H 3Ac-5-Ind V-47 V-48 cPenMeO H H 3Ac-5-Ind V-48 V-49 cPenMeOH H 3Ac, 1Me-5-Ind V-29, V-30 C 420(M⁺ + 1) V-50 cPenMeO Me H 3Me-5-IndV-50 V-51 cPenMeO H H 3Me-5-Ind V-51 V-52 cPenMeO H H 1,3DMe-5Ind V-29,V-30 C 391(M⁺) V-53 cPenMeO H H 1,2,3triMe-5Ind V-22, V-29, V-30 C405(M⁺) V-54 cPenO Me H 4-1HIdz V-54 V-55 cPenO H H 4-1HIdz V-55 V-56cPenO H H 1Me-4-1HIdz V-29, V-30 V-57 cPenO Me H 5-1HIdz V-57 V-58 cPenOH H 5-1HIdz V-58 V-59 cPenO H H 1Me-5-1HIdz V-29, V-30 V-60 cPenO H H1Et-5-1HIdz V-29, V-30 V-61 cPenO H H 1Pr-5-1HIdz V-29, V-30 V-62 cPenOH H 2Me-5-2HIdz V-29, V-30 V-63 cPenMeO H H 6-1HIdz V-57, V-58 V-64cPenMeO H H 1Me-6-1HIdz V-29, V-30 V-65 cPenMeO H H 1Et-5-1HIdz V-29,V-30 V-66 cPenO Me H 3Me-5-1HIdz V-66 V-67 cPenO H H 3Me-5-1HIdz V-67V-68 cPenO Me H 1,3DMe-51HIdz V-68 V-68 cPenO H H 1,3DMe-51HIdz V-69V-69 cPenO H H 3(CHO)-5-1HIdz V-22, V-23 V-70 cPenO H H 3(CHO),1Me-5-1HIdz V-22, V-23 A 4.38 365(M⁺ + 1) V-71 cPenO H H 3OH-5-1HIdzV-22, V-23 V-72 cPenO H H 3OH, 1Me-5-1HIdz V-22, V-23 A 3.71 381(M⁺ + 1)V-73 cPenMeO Me H 5-BT V-73 V-74 cPenMeO H H 5-BT V-74 V-75 cPenMeO H H5-BF V-22, V-23 C 378(M⁺) V-76 cPenMeO H H 2,3DMe-5-BF V-22, V-23 C406(M⁺) V-77 cPenMeO Me H 5-2ABzt V-77 V-78 cPenMeO H H 5-2ABzt V-78V-79 cPenMeO Et H 5-Bzt V-79 V-80 cPenMeO H H 5-Bzt V-80 V-81 cPenMeO MeH 2Me-5-Bzt V-81 V-82 cPenMeO H H 2Me-5-Bzt V-82 V-83 cPenMeO Et H2,2DMe-5-2ABzt V-83 V-84 cPenMeO H H 2,2DMe-5-2ABzt V-84 V-85 cPenMeO HH 6-2ABzt V-77, V-78 C 397(M⁺ + 1) V-86 cPenMeO H H 6-Bzt V-79, V-80 C453(M⁺ + 1) V-87 cPenMeO H H 2Me-6-Bzt V-81, V-82 C 410(M⁺ + 1) V-88cPenMeO H H

V-88 V-89 cPenMeO H H

V-89

TABLE V-3 V-90 cPenMeO H H

V-29, V-30 C 412 (M⁺ + 1) V-91 cPenMeO H H

V-91 C 414 (M⁺ + 1) V-92 cPenMeO H H

V-29, V-30 C 425 (M⁺ + 1) V-93 cPenO H H

V-22, V-23 B 3.87 368 (M⁺ + 1) V-94 cPenO H H

V-22, V-23 B 3.58 368 (M⁺ + 1) V-95 cPenO H H

V-22, V-23 A 2.57 315 (M⁺ + 1) V-96 cPenO H H

V-22, V-23 A 3.84 351 (M⁺ + 1) V-97 cPenO H H

V-29, V-30 A 4.28 365 (M⁺ + 1) V-98 cPenMeO H H 3-Qu V-22, V-23 C 376(M⁺ + 1) V-99 cPenMeO H H 6-Qu V-22, V-23 C 376 (M⁺ + 1) V-100 cPenO H H6-IQ V-22, V-23 A 2.15 452 (M⁺ + 1) V-101 cPenO H H

V-22, V-23 A 3.74 378 (M⁺ + 1) V-102 cPenMeO H H

V-22, V-23 C 378 (M⁺ + 1) V-103 cHexMeO Et H

V-33 C 406 (M⁺) V-104 cHexMeO H H

V-34 C 378 (M⁺ + 1) V-105 cHexMeO Et H

V-33 C 422 (M⁺) V-106 cHexMeO H H

V-34 C 394 (M⁺) V-107 cHexMeO H H

V-22, V-23 C 455 (M⁺ + 1) V-108 cHexMeO H H

V-22, V-23 C 495 (M⁺ + 1) V-109 cHexMeO H H

V-22, V-23 C 487 (M⁺ + 1) V-110 cPenO H H 3(COOH),1Me-7-1HIdz V-22, V-23A 3.99 409 (M⁺ + 1) V-111 cPenO H H 3(COOH),1Me-5-1HIdz V-22, V-23 A3.75 409 (M⁺ + 1) V-112 cPenO H H 3(COOH),2Me-5-2HIdz V-22, V-23 A 3.96409 (M⁺ + 1) V-113 cPenO H H 3(COOH),2Me-7-2HIdz V-22, V-23 A 3.80 409(M⁺ + 1) V-114 cPenO H H 3(COOH)-7-1HIdz V-22, V-23 A 3.66 395 (M⁺ + 1)V-115 ePenO H H 3(COOH)-5-1HIdz V-22, V-23 A 3.49 395 (M⁺ + 1)

Examples W-1 to W-25 Synthesis of 6-bromocinnoline (Intermediate 96)

The title compound (Intermediate 96, 134 mg) was obtained fromcommercially available 4-bromo-2-iodoaniline (711 mg, Ald) by a methodknown from literature (Kimball, D. et al., Organic Letter, 2000, p.3825).

Synthesis of 7-bromoquinazoline (Intermediate 97)

The title compound (Intermediate 97, 921 mg) was obtained fromcommercially available quinazoline (2.11 g, WAKO) by a known methoddescribed in a publication (Dalby, B. et al., Synthesis, 2002, p. 83).

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification are shown inTable-W-1 and Table-W-2.

TABLE W-1

LCMS Exp. RxO Y Zx AR Syn method RTime Mass W-1 cPenMeO H H

V-22, V-23 C 366 (M⁺ + 1) W-2 cPenMeO H H

V-22, V-23 C 383 (M⁺ + 1) W-3 cPenMeO H H

V-22, V-23 C 365 (M⁺ + 1) W-4 cPenMeO H H

V-22, V-23 C 380 (M⁺ + 1) W-5 cPenMeO H H

V-22, V-23 C 366 (M⁺ + 1) W-6 cPenMeO H H

V-22, V-23 C 380 (M⁺ + 1) W-7 cPenMeO H H

V-22, V-23 C 381 (M⁺ + 1) W-8 cPenMeO H H

V-22, V-23 C 398 (M⁺ + 1) W-9 cPenMeO H H

V-22, V-23 C 382 (M⁺ + 1) W-10 cPenMeO H H

V-22, V-23 C 366 (M⁺ + 1) W-11 cPenMeO H H

V-22, V-23 C 377 (M⁺ + 1) W-12 cPenO H H

V-22, V-23 A 3.97 363 (M⁺ + 1) W-13 cPenO H H

V-22, V-23 A 4.06 363 (M⁺ + 1) W-14 cPenMeO H H

V-22, V-23 C 380 (M⁺ + 1) W-15 cPenO H H

V-22, V-23 C 355 (M⁺ + 1) W-16 cPenMeO H H

V-22, V-23 C 397 (M⁺ + 1) W-17 cPenMeO H H

V-22, V-23 C 381 (M⁺ + 1) W-18 cPenMeO H H

V-22, V-23 C 380 (M⁺ + 1)

TABLE W-2 W-19 cPenMeO H H

V-22, V-23 C 381 (M⁺ + 1) W-20 cPenMeO H H

V-22, V-23 C 398 (M⁺ + 1) W-21 cPenMeO H H

V-22, V-23 C 382 (M⁺ + 1) W-22 cPenO H H

V-22, V-23 C 351 (M⁺ + 1) W-23 cPenO H H

V-22, V-23 C 353 (M⁺ + 1) W-24 cPenO H H

V-22, V-23 C 353 (M⁺ + 1) W-25 cPenO H H

V-22, V-23 C 367 (M⁺ + 1)

Example X-1 Synthesis of ethyl3-[2-cyclopentyloxy-5-(naphthalen-2-yl)phenyl]acrylate (Intermediate 98)

According to the procedure described in the synthesis method ofIntermediate 7 provided that the reaction was carried out for 1 hour,Compound No. D-20 (396 mg), ethyl diethylphosphonoacetate (288 μl), and60% sodium hydride (59 mg) were reacted and treated to obtain the titlecompound (Intermediate 98, 428 mg).

Synthesis of ethyl3-[2-cyclohexylmethyloxy-5-(naphthalen-1-yl)phenyl]propionate (CompoundNo. X-1)

According to the procedure described in the synthesis method ofIntermediate B-99 with the modifications that the reaction was carriedout at 50° C. for 5 hours, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate=10:1), Intermediate 98 (361mg) and Raney 2800 nickel (380 mg) were reacted and treated to obtainthe title compound (Compound No. X-1, 397 mg).

Example X-2 Synthesis of3-[2-cyclohexylmethyloxy-5-(naphthalen-1-yl)phenyl]propionic acid(Compound No. X-2)

According to the procedure described in the synthesis method ofIntermediate 9 provided that the reaction was carried out for 2.5 hours,Compound No. X-1 (390 mg) and 2 N aqueous sodium hydroxide (1.1 ml) werereacted and treated to obtain the title compound (Compound No. X-2, 338mg).

Examples X-1 to X-4

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-X-1.

TABLE X-1

RxO AR LCMS Exp. RxO Y positio AR Syn position method RTime Mass X-1cPenO Et 2 2-Nap X-1 5 X-2 cPenO H 2 2-Nap X-2 5 C 347 (M⁺ + 1) X-3cPenO H 2 1Me-5-Ind X-1, X-2 5 C 350 (M⁺ + 1) X-4 cPenO H 2 1Me-5-1HIdzX-1, X-2 5 C 351 (M⁺ + 1)

Reference Examples Intermediates Aa-1 to Aa-47 Synthesis of methyl3-[3-(naphthalen-2-yl)-4-trifluoromethanesulfonylphenyl]-propionate(Intermediate Aa-1)

A solution of Intermediate 41 (4.34 g) in dehydrated pyridine (120 ml)was added with trifluoromethanesulfonic anhydride (2.6 ml, ALD) underice cooling, then warmed to room temperature, and stirred for 4 hours.The reaction mixture was concentrated under reduced pressure, and thenextracted with ethyl acetate (800 ml). The organic layer was washedsuccessively with 1 N hydrochloric acid, saturated aqueous ammoniumchloride and saturated brine, and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:ethyl acetate=6:1) to obtain the titlecompound (Intermediate Aa-1, 4.98 g).

Typical examples of the reaction intermediates including those mentionedabove, that can be obtained by reacting and treating correspondingstarting compounds according to the synthesis method of IntermediateAa-1, are shown in Table-Aa-1.

In the column indicated as “Mass” in the table, data of mass spectrameasured by fast atom bombardment mass spectrometry (FAB-MS) are shown.

TABLE Aa-1

Exp. AR Mass Aa-1 2-Nap 439 (M⁺ + 1) Aa-2 5-Ind 428 (M⁺ + 1) Aa-31Me-5-Ind 442 (M⁺ + 1) Aa-4 5-1HIdz 429 (M⁺ + 1) Aa-5 1Me-5-1HIdz 443(M⁺ + 1) Aa-6 5-BF 432 (M⁺ + 1) Aa-7 3-Qu 440 (M⁺ + 1) Aa-8 1-Nap 439(M⁺ + 1) Aa-9 6(MeO)-2-Nap 469 (M⁺ + 1) Aa-10 6(NMe₂)-2-Nap 482 (M⁺ + 1)Aa-11 4-Ind 428 (M⁺ + 1) Aa-12 1Me-4-Ind 442 (M⁺ + 1) Aa-13 6-Ind 428(M⁺ + 1) Aa-14 1Me-6-Ind 442 (M⁺ + 1) Aa-15 2-Ind 428 (M⁺ + 1) Aa-161Me-2-Ind 442 (M⁺ + 1) Aa-17 3-Ind 428 (M⁺ + 1) Aa-18 1Me-3-Ind 442(M⁺ + 1) Aa-19 1iPr-5-Ind 470 (M⁺ + 1) Aa-20 1cPen-5-Ind 496 (M⁺ + 1)Aa-21 3Me-5-Ind 442 (M⁺ + 1) Aa-22 1,3DMe-5Ind 456 (M⁺ + 1) Aa-231,2,3triMe-5Ind 470 (M⁺ + 1) Aa-24 4-1HIdz 429 (M⁺ + 1) Aa-251Me-4-1HIdz 443 (M⁺ + 1) Aa-26 5-1HIdz 429 (M⁺ + 1) Aa-27 1Me-5-1HIdz443 (M⁺ + 1) Aa-28 1Et-5-1HIdz 457 (M⁺ + 1) Aa-29 1Pr-5-1HIdz 471(M⁺ + 1) Aa-30 2Me-5-2HIdz 443 (M⁺ + 1) Aa-31 6-1HIdz 429 (M⁺ + 1) Aa-321Me-6-1HIdz 443 (M⁺ + 1) Aa-33 3Me-5-1HIdz 443 (M⁺ + 1) Aa-341,3DMe-5-1HIdz 457 (M⁺ + 1) Aa-35 5-BT 445 (M⁺ + 1) Aa-36 2,3DMe-5-BF457 (M⁺ + 1) Aa-37 5-2ABzt 461 (M⁺ + 1) Aa-38 5-Bzt 456 (M⁺ + 1) Aa-392Me-5-Bzt 460 (M⁺ + 1) Aa-40 2,2DMe-5-2ABzt 489 (M⁺ + 1) Aa-41 6-2ABzt461 (M⁺ + 1) Aa-42 6-Bzt 456 (M⁺ + 1) Aa-43 2Me-6-Bzt 460 (M⁺ + 1) Aa-446-Qu 440 (M⁺ + 1) Aa-45 6-IQ 440 (M⁺ + 1) Aa-46 2-BF 429 (M⁺ + 1) Aa-472-BT 445 (M⁺ + 1)

Example Ca-1 Synthesis of methyl3-[4-(phenyl)-3-(naphthalen-2-yl)phenyl]propionate (Compound No. Ca-1)

Compound No. Aa-1 (138.4 mg, corresponding to the substance mentioned inthe column of SM1 in Table-Ca-1 mentioned later), phenylboronic acid(71.3 mg, corresponding to the substance mentioned in the column of SM 2mentioned in Table-Ca-1 mentioned later), cesium carbonate (254.9 mg),PdCl₂(dppf) (25.6 mg) were added with toluene (600 μl), methanol (1.2ml), and water (1.2 ml), and stirred at 80° C. for 17 hours undernitrogen atmosphere. The reaction mixture was added with ethyl acetate(30 ml), washed successively with water and saturated brine. The organiclayer was dried, and then the solvent was evaporated under reducedpressure. The residue was purified by flash column chromatography(hexane:ethyl acetate=8:1) to obtain the title compound (Compound No.Ca-1, 140.6 mg).

Example Ca-2 Synthesis of3-[4-phenyl-3-(naphthalen-2-yl)phenyl]propionic acid (Compound No. Ca-2)

A solution of Compound Ca-1 (137.7 mg) in methanol (4.0 ml) was addedwith 2 N aqueous sodium hydroxide (720 μl), and stirred at 60° C. for 16hours. The reaction mixture was concentrated under reduced pressure,then made acidic with 5% aqueous hydrochloric acid under ice cooling,and extracted with ethyl acetate (50 ml). The organic layer was washedwith saturated brine, and dried, and then the solvent was evaporatedunder reduced pressure to obtain the title compound (Compound No. Ca-2,108 mg).

Examples Ca-1 to Ca-270 and Examples Cb-1 to Cb-95

Typical examples of the compounds of the present invention includingthose mentioned in the examples described above, that can be obtained byreacting and treating corresponding starting compounds according to themethods described in Examples Ca-1 and Ca-2, are shown in Table-Ca-1 toTable-Ca-5, Table-Cb-1 and Table-Cb-2.

The substances mentioned in the columns of “SM1” in the tablescorrespond to reaction intermediates, and those mentioned in the columnsof “SM2” in the tables correspond to the boronic acid reagent used inExample Ca-1. The boronic acid reagents shown with the symbols of “BRA(number)” mentioned in the columns of “SM2” are those mentioned inTable-Ba-1 and Table-Ba-2. The regents for which cells of the columns of“Manufacturer” in the tables are blank are synthesized according to amethod described in ordinary chemical literatures.

TABLE Ba-1 Reagen Name of reagent Manufacturer BRA1Naphthalene-2-boronic TCI acid BRA2 (1H-Indol-5-yl) boronic Frontieracid BRA3 (1-Methyl-1H-indol- Frontier 5-yl) boronic acid BRA4(1-Ethyl-1H-indol- 5-yl) boronic acid BRA5 (1H-Indazol-5-yl) boronicacid BRA6 (1-Methyl-1H-indazol- 5-yl) boronic acid BRA7(1-Ethyl-1H-indazol- 5-yl) boronic acid BRA8 (2-Methyl-2H-indazol- 5-yl)boronic acid BRA9 Benzothiazole-6-yl- 4,4,5,5-tetramethyl-1,3,2-dioxaborolan BRA10 Quinoline-3-boronic acid Frontier BRA11Quinoline-6-yl-4,4,5,5- Ald tetramethyl- 1,3,2-dioxaborolan BRA12Isoquinoline-6-yl- 4,4,5,5-tetramethyl- 1,3,2-dioxaborolan BRA13 Methylboronic acid Ald BRA14 Phenyl boronic acid Ald BRA15 4-Hydroxyphenylboronic Ald acid BRA16 Naphthalene-1-boronic Ald acid BRA173,5-Bis(trifluoromethyl) TCI phenyl boronic acid BRA18Benzo[b]furan-2-boronic Ald acid BRA19 4-Methoxypheny boronic Ald acidBRA20 2-Methylpropyl boronic Ald acid BRA21 4-(Dimethylamino) phenyl Aldboronic acid BRA22 4-Fluorophenyl boronic TCI acid BRA23 Cyclopropylboronic acid BRA24 6-Ethoxynaphthalene-2- Ald boronic acid BRA25Benzo[b]thiophene- LANC 2-boronic acid BRA26 Pyridine-4-boronic acid ALDBRA27 Dibenzofuran-2-boronic Ald acid BRA28 Cyclopentyl boronic acidLANC BRA29 4-Methylphenyl boronic Ald acid BRA30 4-Chlorophenyl boronicAld acid BRA31 1-n-Butyl boronic acid Ald BRA32 2-Fluorophenyl boronicacid Ald BRA33 3-Fluorophenyl boronic acid Ald BRA34 4-Fluorophenylboronic acid Ald BRA35 2-Furyl boronic acid Ald BRA36 2-Thienyl boronicacid Ald BRA37 3-Methoxyphenyl boronic acid Ald BRA38 2-Methoxyphenylboronic acid BRA39 2-(Trifluoromethyl) phenyl boronic acid BRA403-(Trifluoromethyl) phenyl boronic acid BRA41 4-(Trifluoromethyl) phenylboronic acid BRA42 Indan-2-yl-4,4,5,5-tetramethyl- 1,3,2-dioxaborolaneBRA43 4-Methylindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA445-Methylindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane

TABLE Ba-2 Reagent Name of reagent Manufacture BRA454,7-Dimethylindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA465,6-Dimethylindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA475-Fluoroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA484-Fluoroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA494,7-Difluoroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA505,6-Difluoroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA514-Chloroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA525-Chloroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA534,7-Dichloroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA545,6-Dichloroindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA554-Methoxyindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA565-Methoxyindan-2-yl-4,4,5,5- tetramethyl-1,3,2-dioxaborolane BRA575,6-Dimethoxyindan-2-yl- 4,4,5,5-tetramethyl-1,3,2- BRA58 Cyclohexylboronic acid Ald BRA59 2-Methylphenyl boronic acid Ald BRA603-Methylphenyl boronic acid Ald BRA61 2-Chlorophenyl boronic acid AldBRA62 3-Chlorophenyl boronic acid Ald BRA63 2,3-Bis(trifluoromethyl)phenyl boronic acid BRA64 2,4-Bis(trifluoromethyl) phenyl boronic acidBRA65 2,5-Bis(trifluoromethyl) phenyl boronic acid BRA663,4-Bis(trifluoromethyl) phenyl boronic acid BRA67 3-Furyl boronic acidAld BRA68 3-Thienyl boronic Ald acid BRA69 Pyridine-2-yl-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane BRA70 Pyridine-3-boronic Aldacid BRA71 2,3-Dimethylphenyl Ald boronic acid BRA72 2,5-DimethylphenylAld boronic acid BRA73 3,5-Dimethylphenyl Ald boronic acid BRA742,3-DiChlorophenyl Ald boronic acid BRA75 2,4-DiChlorophenyl Ald boronicacid BRA76 2,5-DiChlorophenyl Ald boronic acid BRA77 2,6-DiChlorophenylAcros boronic acid BRA78 3,4-DiChlorophenyl Ald boronic acid BRA793,5-DiChlorophenyl Ald boronic acid BRA80 2,3-Difluorophenyl Ald boronicacid BRA81 2,4-Difluorophenyl Ald boronic acid BRA82 2,5-DifluorophenylAld boronic acid BRA83 2,6-Difluorophenyl Ald boronic acid BRA843,4-Difluorophenyl Ald boronic acid BRA85 3,5-Difluorophenyl Ald boronicacid BRA86 2-(Dimethylamino) Digital phenyl boronic acid BRA873-(Dimethylamino) Digital phenyl boronic acid BRA88 4-Phenoxy phenyl Aldboronic acid

TABLE Ca-1

LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Ca-1 Ph Me H 2-Nap Aa-1BRA14 D N.D Ca-2 Ph H H 2-Nap Ca-1 — C 353 (M⁺ + 1) Ca-3 Ph Me H 5-IndAa-2 BRA14 C 356 (M⁺ + 1) Ca-4 Ph H H 5-Ind Ca-3 — C 342 (M⁺ + 1) Ca-5Ph Me H 1Me-5-Ind Aa-3 BRA14 C 370 (M⁺ + 1) Ca-6 Ph H H 1Me-5-Ind Ca-5 —C 356 (M⁺ + 1) Ca-7 Ph H H 5-1HIdz Aa-4 BRA14 C 343 (M⁺ + 1) Ca-8 Ph MeH 1Me-5-1HIdz Aa-5 BRA14 C 371 (M⁺ + 1) Ca-9 Ph H H 1Me-5-1HIdz Ca-8 — C357 (M⁺ + 1) Ca-10 Ph H H 5-BF Aa-6 BRA14 C 342 (M⁺ + 1) Ca-11 Ph H H3-Qu Aa-7 BRA14 C 354 (M⁺ + 1) Ca-12 Ph H H 1-Nap Aa-8 BRA14 C 353(M⁺ + 1) Ca-13 Ph H H 6(OMe)-2-Nap Aa-9 BRA14 C 383 (M⁺ + 1) Ca-14 Ph HH 6(NMe2)-2-Nap Aa-10 BRA14 C 396 (M⁺ + 1) Ca-15 Ph H H 4-Ind Aa-11BRA14 C 342 (M⁺ + 1) Ca-16 Ph H H 1Me-4-Ind Aa-12 BRA14 C 356 (M⁺ + 1)Ca-17 Ph H H 6-Ind Aa-13 BRA14 C 342 (M⁺ + 1) Ca-18 Ph H H 1Me-6-IndAa-14 BRA14 C 356 (M⁺ + 1) Ca-19 Ph H H 2-Ind Aa-15 BRA14 C 342 (M⁺ + 1)Ca-20 Ph H H 1Me-2-Ind Aa-16 BRA14 C 356 (M⁺ + 1) Ca-21 Ph H H 3-IndAa-17 BRA14 C 342 (M⁺ + 1) Ca-22 Ph H H 1Me-3-Ind Aa-18 BRA14 C 356(M⁺ + 1) Ca-23 Ph H H 1iPr-5-Ind Aa-19 BRA14 C 384 (M⁺ + 1) Ca-24 Ph H H1cPen-5-Ind Aa-20 BRA14 C 410 (M⁺ + 1) Ca-25 Ph H H 3Me-5-Ind Aa-21BRA14 C 356 (M⁺ + 1) Ca-26 Ph H H 1,3DMe-5Ind Aa-22 BRA14 C 370 (M⁺ + 1)Ca-27 Ph H H 1,2,3triMe-5Ind Aa-23 BRA14 C 384 (M⁺ + 1) Ca-28 Ph H H4-1HIdz Aa-24 BRA14 C 343 (M⁺ + 1) Ca-29 Ph H H 1Me-4-1HIdz Aa-25 BRA14C 357 (M⁺ + 1) Ca-30 Ph H H 5-1HIdz Aa-26 BRA14 C 343 (M⁺ + 1) Ca-31 PhH H 1Me-5-1HIdz Aa-27 BRA14 C 357 (M⁺ + 1) Ca-32 Ph H H 1Et-5-1HIdzAa-28 BRA14 C 371 (M⁺ + 1) Ca-33 Ph H H 1Pr-5-1HIdz Aa-29 BRA14 C 385(M⁺ + 1) Ca-34 Ph H H 2Me-5-2HIdz Aa-30 BRA14 C 357 (M⁺ + 1) Ca-35 Ph HH 6-1HIdz Aa-31 BRA14 C 343 (M⁺ + 1) Ca-36 Ph H H 1Me-6-1HIdz Aa-32BRA14 C 357 (M⁺ + 1) Ca-37 Ph H H 3Me-5-1HIdz Aa-33 BRA14 C 357 (M⁺ + 1)Ca-38 Ph H H 1,3DMe-5-1HIdz Aa-34 BRA14 C 371 (M⁺ + 1) Ca-39 Ph H H 5-BTAa-35 BRA14 C 359 (M⁺ + 1) Ca-40 Ph H H 2,3DMe-5-BF Aa-36 BRA14 C 387(M⁺ + 1) Ca-41 Ph H H 5-2ABzt Aa-37 BRA14 C 375 (M⁺ + 1) Ca-42 Ph H H5-Bzt Aa-38 BRA14 C 360 (M⁺ + 1) Ca-43 Ph H H 2Me-5-Bzt Aa-39 BRA14 C374 (M⁺ + 1) Ca-44 Ph H H 2,2DMe-5-2ABzt Aa-40 BRA14 C 403 (M⁺ + 1)Ca-45 Ph H H 6-2ABzt Aa-41 BRA14 C 375 (M⁺ + 1) Ca-46 Ph H H 6-Bzt Aa-42BRA14 C 360 (M⁺ + 1) Ca-47 Ph H H 2Me-6-Bzt Aa-43 BRA14 C 374 (M⁺ + 1)Ca-48 Ph H H 6-Qu Aa-44 BRA14 C 354 (M⁺ + 1) Ca-49 Ph H H 6-IQ Aa-45BRA14 C 354 (M⁺ + 1) Ca-50 Ph H H 2-BF Aa-46 BRA14 C 342 (M⁺ + 1)

TABLE Ca-2 LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Ca-51 Ph H H2-BT Aa-47 BRA14 C 359 (M⁺ + 1) Ca-52 4MeOPh H H 2-Nap Aa-1 BRA19 C 383(M⁺ + 1) Ca-53 4MeOPh H H 1Me-5-Ind Aa-3 BRA19 C 386 (M⁺ + 1) Ca-544MeOPh H H 5-1HIdz Aa-4 BRA19 C 373 (M⁺ + 1) Ca-55 4MeOPh H H1Me-5-1HIdz Aa-5 BRA19 C 387 (M⁺ + 1) Ca-56 4MeOPh H H 3-Qu Aa-7 BRA19 C384 (M⁺ + 1) Ca-57 4MeOPh H H 1Et-5-1HIdz Aa-28 BRA19 C 401 (M⁺ + 1)Ca-58 3MeOPh H H 5-Ind Aa-2 BRA37 C 372 (M⁺ + 1) Ca-59 3MeOPh H H1Me-5-Ind Aa-3 BRA37 C 386 (M⁺ + 1) Ca-60 3MeOPh H H 5-1HIdz Aa-4 BRA37C 373 (M⁺ + 1) Ca-61 3MeOPh H H 1Me-5-1HIdz Aa-5 BRA37 C 387 (M⁺ + 1)Ca-62 3MeOPh H H 3-Qu Aa-7 BRA37 C 384 (M⁺ + 1) Ca-63 3MeOPh H H1Et-5-1HIdz Aa-28 BRA37 C 401 (M⁺ + 1) Ca-64 2MeOPh H H 2-Nap Aa-1 BRA38C 383 (M⁺ + 1) Ca-65 2MeOPh H H 5-Ind Aa-2 BRA38 C 372 (M⁺ + 1) Ca-662MeOPh H H 1Me-5-Ind Aa-3 BRA38 C 386 (M⁺ + 1) Ca-67 2MeOPh H H 5-1HIdzAa-4 BRA38 C 373 (M⁺ + 1) Ca-68 2MeOPh H H 1Me-5-1HIdz Aa-5 BRA38 C 387(M⁺ + 1) Ca-69 2MeOPh H H 5-Bzt Aa-38 BRA38 C 390 (M⁺ + 1) Ca-70 2MeOPhH H 3-Qu Aa-7 BRA38 C 384 (M⁺ + 1) Ca-71 2MeOPh H H 1Et-5-1HIdz Aa-28BRA38 C 401 (M⁺ + 1) Ca-72 2MePh H H 2-Nap Aa-1 BRA59 C 367 (M⁺ + 1)Ca-73 2MePh H H 5-Ind Aa-2 BRA59 C 356 (M⁺ + 1) Ca-74 2MePh H H1Me-5-Ind Aa-3 BRA59 C 370 (M⁺ + 1) Ca-75 2MePh H H 5-1HIdz Aa-4 BRA59 C357 (M⁺ + 1) Ca-76 2MePh H H 1Me-5-1HIdz Aa-5 BRA59 C 371 (M⁺ + 1) Ca-772MePh H H 5-Bzt Aa-38 BRA59 C 374 (M⁺ + 1) Ca-78 3MePh H H 2-Nap Aa-1BRA60 C 367 (M⁺ + 1) Ca-79 3MePh H H 5-Ind Aa-2 BRA60 C 356 (M⁺ + 1)Ca-80 3MePh H H 5-1HIdz Aa-4 BRA60 C 357 (M⁺ + 1) Ca-81 3MePh H H1Me-5-1HIdz Aa-5 BRA60 C 371 (M⁺ + 1) Ca-82 3MePh H H 5-Bzt Aa-38 BRA60C 374 (M⁺ + 1) Ca-83 3MePh H H 1Et-5-1HIdz Aa-28 BRA60 C 385 (M⁺ + 1)Ca-84 4MePh H H 2-Nap Aa-1 BRA29 C 367 (M⁺ + 1) Ca-85 4MePh H H 5-IndAa-2 BRA29 C 356 (M⁺ + 1) Ca-86 4MePh H H 1Me-5-Ind Aa-3 BRA29 C 370(M⁺ + 1) Ca-87 4MePh H H 5-1HIdz Aa-4 BRA29 C 357 (M⁺ + 1) Ca-88 4MePh HH 1Me-5-1HIdz Aa-5 BRA29 C 371 (M⁺ + 1) Ca-89 4MePh H H 5-Bzt Aa-38BRA29 C 374 (M⁺ + 1) Ca-90 4MePh H H 3-Qu Aa-7 BRA29 C 368 (M⁺ + 1)Ca-91 4MePh H H 1Et-5-1HIdz Aa-28 BRA29 C 385 (M⁺ + 1) Ca-92 2,3DMePh HH 5-Ind Aa-2 BRA71 C 370 (M⁺ + 1) Ca-93 2,3DMePh H H 1Me-5-Ind Aa-3BRA71 C 384 (M⁺ + 1) Ca-94 2,3DMePh H H 5-1HIdz Aa-4 BRA71 C 371(M⁺ + 1) Ca-95 2,3DMePh H H 1Me-5-1HIdz Aa-5 BRA71 C 385 (M⁺ + 1) Ca-962,3DMePh H H 1Et-5-1HIdz Aa-28 BRA71 C 399 (M⁺ + 1) Ca-97 2,5DMePh H H2-Nap Aa-1 BRA72 C 381 (M⁺ + 1) Ca-98 2,5DMePh H H 1Me-5-Ind Aa-3 BRA72C 384 (M⁺ + 1) Ca-99 2,5DMePh H H 5-1HIdz Aa-4 BRA72 C 371 (M⁺ + 1)Ca-100 2,5DMePh H H 1Me-5-1HIdz Aa-5 BRA72 C 385 (M⁺ + 1) Ca-1012,5DMePh H H 1Et-5-1HIdz Aa-28 BRA72 C 399 (M⁺ + 1) Ca-102 3,5DMePh H H2-Nap Aa-1 BRA73 C 381 (M⁺ + 1) Ca-103 3,5DMePh H H 1Me-5-Ind Aa-3 BRA73C 384 (M⁺ + 1) Ca-104 3,5DMePh H H 1Me-5-1HIdz Aa-5 BRA73 C 385 (M⁺ + 1)Ca-105 2CF₃Ph H H 2-Nap Aa-1 BRA39 C 421 (M⁺ + 1)

TABLE Ca-3 LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Ca-106 2CF₃PhH H 5-Ind Aa-2 BRA39 C 410 (M⁺ + 1) Ca-107 2CF₃Ph H H 1Me-5-1HIdz Aa-5BRA39 C 425 (M⁺ + 1) Ca-108 2CF₃Ph H H 5-Bzt Aa-38 BRA39 C 428 (M⁺ + 1)Ca-109 2CF₃Ph H H 3-Qu Aa-7 BRA39 C 422 (M⁺ + 1) Ca-110 2CF₃Ph H H1Et-5-1HIdz Aa-28 BRA39 C 439 (M⁺ + 1) Ca-111 3CF₃Ph H H 2-Nap Aa-1BRA40 C 421 (M⁺ + 1) Ca-112 3CF₃Ph H H 5-Ind Aa-2 BRA40 C 410 (M⁺ + 1)Ca-113 3CF₃Ph H H 1Me-5-Ind Aa-3 BRA40 C 424 (M⁺ + 1) Ca-114 3CF₃Ph H H1Me-5-1HIdz Aa-5 BRA40 C 425 (M⁺ + 1) Ca-115 3CF₃Ph H H 5-Bzt Aa-38BRA40 C 428 (M⁺ + 1) Ca-116 3CF₃Ph H H 3-Qu Aa-7 BRA40 C 422 (M⁺ + 1)Ca-117 4CF₃Ph H H 5-Ind Aa-2 BRA41 C 410 (M⁺ + 1) Ca-118 4CF₃Ph H H5-1HIdz Aa-4 BRA41 C 411 (M⁺ + 1) Ca-119 4CF₃Ph H H 1Me-5-1HIdz Aa-5BRA41 C 425 (M⁺ + 1) Ca-120 4CF₃Ph H H 5-Bzt Aa-38 BRA41 C 428 (M⁺ + 1)Ca-121 4CF₃Ph H H 3-Qu Aa-7 BRA41 C 422 (M⁺ + 1) Ca-122 4CF₃Ph H H1Et-5-1HIdz Aa-28 BRA41 C 439 (M⁺ + 1) Ca-123 2ClPh H H 5-Ind Aa-2 BRA41C 376 (M⁺ + 1) Ca-124 2ClPh H H 5-1HIdz Aa-4 BRA61 C 377 (M⁺ + 1) Ca-1252ClPh H H 1Me-5-1HIdz Aa-5 BRA61 C 391 (M⁺ + 1) Ca-126 2ClPh H H 3-QuAa-7 BRA61 C 388 (M⁺ + 1) Ca-127 3ClPh H H 2-Nap Aa-1 BRA62 C 387(M⁺ + 1) Ca-128 3ClPh H H 1Me-5-Ind Aa-3 BRA62 C 390 (M⁺ + 1) Ca-1293ClPh H H 5-1HIdz Aa-4 BRA62 C 377 (M⁺ + 1) Ca-130 3ClPh H H 1Me-5-1HIdzAa-5 BRA62 C 391 (M⁺ + 1) Ca-131 3ClPh H H 5-Bzt Aa-38 BRA62 C 394(M⁺ + 1) Ca-132 4ClPh H H 5-Ind Aa-2 BRA30 C 376 (M⁺ + 1) Ca-133 4ClPh HH 1Me-5-Ind Aa-3 BRA30 C 390 (M⁺ + 1) Ca-134 4ClPh H H 1Me-5-1HIdz Aa-5BRA30 C 391 (M⁺ + 1) Ca-135 4ClPh H H 5-Bzt Aa-38 BRA30 C 394 (M⁺ + 1)Ca-136 2,3DClPh H H 5-Ind Aa-2 BRA74 C 411 (M⁺ + 1) Ca-137 2,3DClPh H H1Me-5-Ind Aa-3 BRA74 C 425 (M⁺ + 1) Ca-138 2,3DClPh H H 1Me-5-1HIdz Aa-5BRA74 C 426 (M⁺ + 1) Ca-139 2,4DClPh H H 5-Ind Aa-2 BRA75 C 411 (M⁺ + 1)Ca-140 2,4DClPh H H 1Me-5-1HIdz Aa-5 BRA75 C 426 (M⁺ + 1) Ca-1412,4DClPh H H 5-Bzt Aa-38 BRA75 C 429 (M⁺ + 1) Ca-142 2,5DClPh H H1Me-5-Ind Aa-3 BRA76 C 425 (M⁺ + 1) Ca-143 2,5DClPh H H 1Me-5-1HIdz Aa-5BRA76 C 426 (M⁺ + 1) Ca-144 2,6DClPh H H 1Me-5-1HIdz Aa-5 BRA77 C 426(M⁺ + 1) Ca-145 3,4DClPh H H 2-Nap Aa-1 BRA78 C 421 (M⁺ + 1) Ca-1463,4DClPh H H 5-Ind Aa-2 BRA78 C 411 (M⁺ + 1) Ca-147 3,4DClPh H H1Me-5-Ind Aa-3 BRA78 C 425 (M⁺ + 1) Ca-148 3,4DClPh H H 1Me-5-1HIdz Aa-5BRA78 C 426 (M⁺ + 1) Ca-149 3,5DClPh H H 2-Nap Aa-1 BRA79 C 421 (M⁺ + 1)Ca-150 3,5DClPh H H 1Me-5-Ind Aa-3 BRA79 C 425 (M⁺ + 1) Ca-151 3,5DClPhH H 1Me-5-1HIdz Aa-5 BRA79 C 426 (M⁺ + 1) Ca-152 2FPh H H 2-Nap Aa-1BRA32 C 371 (M⁺ + 1) Ca-153 2FPh H H 1Me-5-Ind Aa-3 BRA32 C 374 (M⁺ + 1)Ca-154 2FPh H H 5-1HIdz Aa-4 BRA32 C 361 (M⁺ + 1) Ca-155 2FPh H H1Me-5-1HIdz Aa-5 BRA32 C 375 (M⁺ + 1) Ca-156 2FPh H H 5-Bzt Aa-38 BRA32C 378 (M⁺ + 1) Ca-157 2FPh H H 3-Qu Aa-7 BRA32 C 372 (M⁺ + 1) Ca-1583FPh H H 5-Ind Aa-2 BRA33 C 360 (M⁺ + 1) Ca-159 3FPh H H 5-1HIdz Aa-4BRA33 C 361 (M⁺ + 1) Ca-160 3FPh H H 1Me-5-1HIdz Aa-5 BRA33 C 375 (M⁺ +1)

TABLE Ca-4 LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Ca-161 3FPh HH 3-Qu Aa-7 BRA33 C 372 (M⁺ + 1) Ca-162 4FPh H H 2-Nap Aa-1 BRA34 C 371(M⁺ + 1) Ca-163 4FPh H H 5-Ind Aa-2 BRA34 C 360 (M⁺ + 1) Ca-164 4FPh H H5-1HIdz Aa-4 BRA34 C 361 (M⁺ + 1) Ca-165 4FPh H H 1Me-5-1HIdz Aa-5 BRA34C 375 (M⁺ + 1) Ca-166 4FPh H H 3-Qu Aa-7 BRA34 C 372 (M⁺ + 1) Ca-1672,3DFPh H H 2-Nap Aa-1 BRA80 C 389 (M⁺ + 1) Ca-168 2,3DFPh H H 5-IndAa-2 BRA80 C 378 (M⁺ + 1) Ca-169 2,3DFPh H H 1Me-5-1HIdz Aa-5 BRA80 C393 (M⁺ + 1) Ca-170 2,4DFPh H H 2-Nap Aa-1 BRA81 C 389 (M⁺ + 1) Ca-1712,4DFPh H H 5-Ind Aa-2 BRA81 C 378 (M⁺ + 1) Ca-172 2,4DFPh H H 1Me-5-IndAa-3 BRA81 C 392 (M⁺ + 1) Ca-173 2,4DFPh H H 1Me-5-1HIdz Aa-5 BRA81 C393 (M⁺ + 1) Ca-174 2,5DFPh H H 2-Nap Aa-1 BRA82 C 389 (M⁺ + 1) Ca-1752,5DFph H H 1Me-5-Ind Aa-3 BRA82 C 392 (M⁺ + 1) Ca-176 2,5DFPh H H1Me-5-1HIdz Aa-5 BRA82 C 393 (M⁺ + 1) Ca-177 2,6DFPh H H 2-Nap Aa-1BRA83 C 389 (M⁺ + 1) Ca-178 2,6DFPh H H 1Me-5-Ind Aa-3 BRA83 C 392(M⁺ + 1) Ca-179 2,6DFPh H H 5-1HIdz Aa-4 BRA83 C 379 (M⁺ + 1) Ca-1802,6DFPh H H 1Me-5-1HIdz Aa-5 BRA83 C 393 (M⁺ + 1) Ca-181 3,4DFPh H H2-Nap Aa-1 BRA84 C 389 (M⁺ + 1) Ca-182 3,4DFPh H H 5-Ind Aa-2 BRA84 C378 (M⁺ + 1) Ca-183 3,4DFPh H H 1Me-5-1HIdz Aa-5 BRA84 C 393 (M⁺ + 1)Ca-184 3,5DFPh H H 2-Nap Aa-1 BRA85 C 389 (M⁺ + 1) Ca-185 3,5DFPh H H1Me-5-Ind Aa-3 BRA85 C 392 (M⁺ + 1) Ca-186 3,5DFPh H H 5-1HIdz Aa-4BRA85 C 379 (M⁺ + 1) Ca-187 3,5DFPh H H 1Me-5-1HIdz Aa-5 BRA85 C 393(M⁺ + 1) Ca-188 2,3(CF₃)₂Ph H H 2-Nap Aa-1 BRA63 C 489 (M⁺ + 1) Ca-1892,3(CF₃)₂Ph H H 1Me-5-Ind Aa-3 BRA63 C 492 (M⁺ + 1) Ca-190 2,3(CF₃)₂Ph HH 1Me-5-1HIdz Aa-5 BRA63 C 493 (M⁺ + 1) Ca-191 2,4(CF₃)₂Ph H H 2-NapAa-1 BRA64 C 489 (M⁺ + 1) Ca-192 2,4(CF₃)₂Ph H H 1Me-5-1HIdz Aa-5 BRA64C 493 (M⁺ + 1) Ca-193 2,5(CF₃)₂Ph H H 2-Nap Aa-1 BRA65 C 489 (M⁺ + 1)Ca-194 2,5(CF₃)₂Ph H H 5-Ind Aa-2 BRA65 C 478 (M⁺ + 1) Ca-1952,5(CF₃)₂Ph H H 1Me-5-1HIdz Aa-5 BRA65 C 493 (M⁺ + 1) Ca-196 2,5(CF₃)₂PhH H 3-Qu Aa-7 BRA65 C 490 (M⁺ + 1) Ca-197 3,4(CF₃)₂Ph H H 2-Nap Aa-1BRA66 C 489 (M⁺ + 1) Ca-198 3,4(CF₃)₂Ph H H 1Me-5-Ind Aa-3 BRA66 C 492(M⁺ + 1) Ca-199 3,4(CF₃)₂Ph H H 5-1HIdz Aa-4 BRA66 C 479 (M⁺ + 1) Ca-2003,4(CF₃)₂Ph H H 1Me-5-1HIdz Aa-5 BRA66 C 493 (M⁺ + 1) Ca-201 3,5(CF₃)₂PhH H 5-Ind Aa-2 BRA17 C 478 (M⁺ + 1) Ca-202 3,5(CF₃)₂Ph H H 5-1HIdz Aa-4BRA17 C 479 (M⁺ + 1) Ca-203 3,5(CF₃)₂Ph H H 1Me-5-1HIdz Aa-5 BRA17 C 493(M⁺ + 1) Ca-204 2-Furyl H H 2-Nap Aa-1 BRA35 C 343 (M⁺ + 1) Ca-2052-Furyl H H 5-Ind Aa-2 BRA35 C 332 (M⁺ + 1) Ca-206 2-Furyl H H1Me-5-1HIdz Aa-5 BRA35 C 347 (M⁺ + 1) Ca-207 2-Furyl H H 3-Qu Aa-7 BRA35C 344 (M⁺ + 1) Ca-208 3-Furyl H H 1Me-5-Ind Aa-3 BRA67 C 346 (M⁺ + 1)Ca-209 3-Furyl H H 5-1HIdz Aa-4 BRA67 C 333 (M⁺ + 1) Ca-210 3-Furyl H H1Me-5-1HIdz Aa-5 BRA67 C 347 (M⁺ + 1) Ca-211 2-Thienyl H H 2-Nap Aa-1BRA36 C 359 (M⁺ + 1) Ca-212 2-Thienyl H H 1Me-5-Ind Aa-3 BRA36 C 362(M⁺ + 1) Ca-213 2-Thienyl H H 1Me-5-1HIdz Aa-5 BRA36 C 363 (M⁺ + 1)Ca-214 2-Thienyl H H 1Et-5-1HIdz Aa-28 BRA36 C 377 (M⁺ + 1) Ca-2153-Thienyl H H 5-Ind Aa-2 BRA68 C 348 (M⁺ + 1)

TABLE Ca-5 LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Ca-2163-Thienyl H H 1Me-5-Ind Aa-3 BRA68 C 362 (M⁺ + 1) Ca-217 3-Thienyl H H5-1HIdz Aa-4 BRA68 C 349 (M⁺ + 1) Ca-218 3-Thienyl H H 1Me-5-1HIdz Aa-5BRA68 C 363 (M⁺ + 1) Ca-219 3-Thienyl H H 5-Bzt Aa-38 BRA68 C 366(M⁺ + 1) Ca-220 3-Thienyl H H 3-Qu Aa-7 BRA68 C 360 (M⁺ + 1) Ca-2213-Thienyl H H 1Et-5-1HIdz Aa-28 BRA68 C 377 (M⁺ + 1) Ca-222 2-Py H H5-Ind Aa-2 BRA69 C 343 (M⁺ + 1) Ca-223 2-Py H H 1Me-5-1HIdz Aa-5 BRA69 C358 (M⁺ + 1) Ca-224 2-Py H H 5-Bzt Aa-38 BRA69 C 361 (M⁺ + 1) Ca-2253-Py H H 2-Nap Aa-1 BRA70 C 354 (M⁺ + 1) Ca-226 3-Py H H 5-Ind Aa-2BRA70 C 343 (M⁺ + 1) Ca-227 3-Py H H 1Me-5-Ind Aa-3 BRA70 C 357 (M⁺ + 1)Ca-228 3-Py H H 1Me-5-1HIdz Aa-5 BRA70 C 358 (M⁺ + 1) Ca-229 3-Py H H1Et-5-1HIdz Aa-28 BRA70 C 372 (M⁺ + 1) Ca-230 4-Py H H 2-Nap Aa-1 BRA26C 354 (M⁺ + 1) Ca-231 4-Py H H 5-Ind Aa-2 BRA26 C 343 (M⁺ + 1) Ca-2324-Py H H 1Me-5-Ind Aa-3 BRA26 C 357 (M⁺ + 1) Ca-233 4-Py H H 5-1HIdzAa-4 BRA26 C 344 (M⁺ + 1) Ca-234 4-Py H H 1Me-5-1HIdz Aa-5 BRA26 C 358(M⁺ + 1) Ca-235 4-Py H H 5-Bzt Aa-38 BRA26 C 361 (M⁺ + 1) Ca-236 4-Py HH 3-Qu Aa-7 BRA26 C 355 (M⁺ + 1) Ca-237 4-Py H H 1Et-5-1HIdz Aa-28 BRA26C 372 (M⁺ + 1) Ca-238 2DMAPh H H 2-Nap Aa-1 BRA86 C 396 (M⁺ + 1) Ca-2392DMAPh H H 5-Ind Aa-2 BRA86 C 385 (M⁺ + 1) Ca-240 2DMAPh H H 1Me-5-1HIdzAa-5 BRA86 C 400 (M⁺ + 1) Ca-241 2DMAPh H H 5-Bzt Aa-38 BRA86 C 403(M⁺ + 1) Ca-242 2DMAPh H H 1Et-5-1HIdz Aa-28 BRA86 C 414 (M⁺ + 1) Ca-2433DMAPh H H 1Me-5-Ind Aa-3 BRA87 C 399 (M⁺ + 1) Ca-244 3DMAPh H H 5-1HIdzAa-4 BRA87 C 386 (M⁺ + 1) Ca-245 3DMAPh H H 1Me-5-1HIdz Aa-5 BRA87 C 400(M⁺ + 1) Ca-246 3DMAPh H H 5-Bzt Aa-38 BRA87 C 403 (M⁺ + 1) Ca-2473DMAPh H H 3-Qu Aa-7 BRA87 C 397 (M⁺ + 1) Ca-248 4DMAPh H H 2-Nap Aa-1BRA21 C 396 (M⁺ + 1) Ca-249 4DMAPh H H 1Me-5-Ind Aa-3 BRA21 C 399(M⁺ + 1) Ca-250 4DMAPh H H 1Me-5-1HIdz Aa-5 BRA21 C 400 (M⁺ + 1) Ca-2514DMAPh H H 3-Qu Aa-7 BRA21 C 397 (M⁺ + 1) Ca-252 4DMAPh H H 1Et-5-1HIdzAa-28 BRA21 C 414 (M⁺ + 1) Ca-253 1-Nap H H 2-Nap Aa-1 BRA16 C 403(M⁺ + 1) Ca-254 1-Nap H H 5-Ind Aa-2 BRA16 C 392 (M⁺ + 1) Ca-255 1-Nap HH 1Me-5-1HIdz Aa-5 BRA16 C 407 (M⁺ + 1) Ca-256 1-Nap H H 5-Bzt Aa-38BRA16 C 410 (M⁺ + 1) Ca-257 2-Nap H H 2-Nap Aa-1 BRA1 C 403 (M⁺ + 1)Ca-258 2-Nap H H 1Me-5-Ind Aa-3 BRA1 C 406 (M⁺ + 1) Ca-259 2-Nap H H5-1HIdz Aa-4 BRA1 C 393 (M⁺ + 1) Ca-260 2-Nap H H 1Me-5-1HIdz Aa-5 BRA1C 407 (M⁺ + 1) Ca-261 2-Nap H H 5-Bzt Aa-38 BRA1 C 410 (M⁺ + 1) Ca-2625-Ind H H 2-Nap Aa-1 BRA2 C 392 (M⁺ + 1) Ca-263 5-Ind H H 5-Ind Aa-2BRA2 C 381 (M⁺ + 1) Ca-264 5-Ind H H 1Me-5-1HIdz Aa-5 BRA2 C 396(M⁺ + 1) Ca-265 5-Ind H H 3-Qu Aa-7 BRA2 C 393 (M⁺ + 1) Ca-266 5-Ind H H1Et-5-1HIdz Aa-28 BRA2 C 410 (M⁺ + 1) Ca-267 1Me-5-1HIdz H H 2-Nap Aa-1BRA6 C 407 (M⁺ + 1) Ca-268 1Me-5-1HIdz H H 1Me-5-Ind Aa-3 BRA6 C 410(M⁺ + 1) Ca-269 1Me-5-1HIdz H H 1Me-5-1HIdz Aa-5 BRA6 C 411 (M⁺ + 1)Ca-270 1Me-5-1HIdz H H 5-Bzt Aa-38 BRA6 C 414 (M⁺ + 1)

TABLE Cb-1

LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Cb-1 cPen H H 2-Nap Aa-1BRA28 C 345 (M⁺ + 1) Cb-2 cPen H H 5-Ind Aa-2 BRA28 C 334 (M⁺ + 1) Cb-3cPen H H 1Me-5-Ind Aa-3 BRA28 C 348 (M⁺ + 1) Cb-4 cPen H H 5-1HIdz Aa-4BRA28 C 335 (M⁺ + 1) Cb-5 cPen H H 1Me-5-1HIdz Aa-5 BRA28 C 349 (M⁺ + 1)Cb-6 cPen H H 5-Bzt Aa-38 BRA28 C 352 (M⁺ + 1) Cb-7 cPen H H 3-Qu Aa-7BRA28 C 346 (M⁺ + 1) Cb-8 cPen H H 1Et-5-1HIdz Aa-28 BRA28 C 363(M⁺ + 1) Cb-9 nBu H H 2-Nap Aa-1 BRA31 C 333 (M⁺ + 1) Cb-10 nBu H H5-Ind Aa-2 BRA31 C 322 (M⁺ + 1) Cb-11 nBu H H 1Me-5-1HIdz Aa-5 BRA31 C337 (M⁺ + 1) Cb-12 iBu H H 2-Nap Aa-1 BRA20 C 333 (M⁺ + 1) Cb-13 iBu H H1Me-5-Ind Aa-3 BRA20 C 336 (M⁺ + 1) Cb-14 iBu H H 1Me-5-1HIdz Aa-5 BRA20C 337 (M⁺ + 1) Cb-15 iBu H H 5-Bzt Aa-38 BRA20 C 340 (M⁺ + 1) Cb-16 iBuH H 1Et-5-1HIdz Aa-28 BRA20 C 351 (M⁺ + 1) Cb-17 2-Indan H H 2-Nap Aa-1BRA42 C 393 (M⁺ + 1) Cb-18 2-Indan H H 5-Ind Aa-2 BRA42 C 382 (M⁺ + 1)Cb-19 2-Indan H H 1Me-5-Ind Aa-3 BRA42 C 396 (M⁺ + 1) Cb-20 2-Indan H H5-1HIdz Aa-4 BRA42 C 382 (M⁺ + 1) Cb-21 2-Indan H H 1Me-5-1HIdz Aa-5BRA42 C 397 (M⁺ + 1) Cb-22 2-Indan H H 5-Bzt Aa-38 BRA42 C 400 (M⁺ + 1)Cb-23 2-Indan H H 3-Qu Aa-7 BRA42 C 394 (M⁺ + 1) Cb-24 2-Indan H H1Et-5-1HIdz Aa-28 BRA42 C 411 (M⁺ + 1) Cb-25 4Me-2-Indan H H 5-Ind Aa-2BRA43 C 396 (M⁺ + 1) Cb-26 4Me-2-Indan H H 5-1HIdz Aa-4 BRA43 C 397(M⁺ + 1) Cb-27 4Me-2-Indan H H 1Me-5-1HIdz Aa-5 BRA43 C 411 (M⁺ + 1)Cb-28 4Me-2-Indan H H 3-Qu Aa-7 BRA43 C 408 (M⁺ + 1) Cb-29 5Me-2-Indan HH 2-Nap Aa-1 BRA44 C 407 (M⁺ + 1) Cb-30 5Me-2-Indan H H 5-Ind Aa-2 BRA44C 396 (M⁺ + 1) Cb-31 5Me-2-Indan H H 5-1HIdz Aa-4 BRA44 C 397 (M⁺ + 1)Cb-32 5Me-2-Indan H H 1Me-5-1HIdz Aa-5 BRA44 C 411 (M⁺ + 1) Cb-335Me-2-Indan H H 5-Bzt Aa-38 BRA44 C 414 (M⁺ + 1) Cb-34 5Me-2-Indan H H1Et-5-1HIdz Aa-28 BRA44 C 425 (M⁺ + 1) Cb-35 4,7DMe-2-Indan H H 5-IndAa-2 BRA45 C 410 (M⁺ + 1) Cb-36 4,7DMe-2-Indan H H 5-1HIdz Aa-4 BRA45 C411 (M⁺ + 1) Cb-37 4,7DMe-2-Indan H H 1Me-5-1HIdz Aa-5 BRA45 C 425(M⁺ + 1) Cb-38 5,6DMe-2-Indan H H 2-Nap Aa-1 BRA46 C 421 (M⁺ + 1) Cb-395,6DMe-2-Indan H H 1Me-5-1HIdz Aa-5 BRA46 C 425 (M⁺ + 1) Cb-405F-2-Indan H H 2-Nap Aa-1 BRA47 C 411 (M⁺ + 1) Cb-41 5F-2-Indan H H5-Ind Aa-2 BRA47 C 400 (M⁺ + 1) Cb-42 5F-2-Indan H H 5-1HIdz Aa-4 BRA47C 401 (M⁺ + 1) Cb-43 5F-2-Indan H H 1Me-5-1HIdz Aa-5 BRA47 C 415(M⁺ + 1) Cb-44 5F-2-Indan H H 5-Bzt Aa-38 BRA47 C 418 (M⁺ + 1) Cb-455F-2-Indan H H 3-Qu Aa-7 BRA47 C 412 (M⁺ + 1) Cb-46 5F-2-Indan H H1Et-5-1HIdz Aa-28 BRA47 C 429 (M⁺ + 1) Cb-47 4F-2-Indan H H 2-Nap Aa-1BRA48 C 411 (M⁺ + 1) Cb-48 4F-2-Indan H H 1Me-5-Ind Aa-3 BRA48 C 414(M⁺ + 1) Cb-49 4F-2-Indan H H 1Me-5-1HIdz Aa-5 BRA48 C 415 (M⁺ + 1)Cb-50 4,7DF-2-Indan H H 2-Nap Aa-1 BRA49 C 429 (M⁺ + 1)

TABLE Cb-2 LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Cb-514,7DF-2-Indan H H 1Me-5-Ind Aa-3 BRA49 C 432 (M⁺ + 1) Cb-524,7DF-2-Indan H H 1Me-5-1HIdz Aa-5 BRA49 C 433 (M⁺ + 1) Cb-535,6DF-2-Indan H H 2-Nap Aa-1 BRA50 C 429 (M⁺ + 1) Cb-54 5,6DF-2-Indan HH 5-Ind Aa-2 BRA50 C 418 (M⁺ + 1) Cb-55 5,6DF-2-Indan H H 1Me-5-Ind Aa-3BRA50 C 432 (M⁺ + 1) Cb-56 5,6DF-2-Indan H H 5-1HIdz Aa-4 BRA50 C 419(M⁺ + 1) Cb-57 5,6DF-2-Indan H H 1Me-5-1HIdz Aa-5 BRA50 C 433 (M⁺ + 1)Cb-58 5,6DF-2-Indan H H 5-Bzt Aa-38 BRA50 C 436 (M⁺ + 1) Cb-595,6DF-2-Indan H H 3-Qu Aa-7 BRA50 C 430 (M⁺ + 1) Cb-60 5,6DF-2-Indan H H1Et-5-1HIdz Aa-28 BRA50 C 447 (M⁺ + 1) Cb-61 4Cl-2-Indan H H 5-Ind Aa-2BRA51 C 416 (M⁺ + 1) Cb-62 4Cl-2-Indan H H 1Me-5-1HIdz Aa-5 BRA51 C 431(M⁺ + 1) Cb-63 4Cl-2-Indan H H 5-Bzt Aa-38 BRA51 C 434 (M⁺ + 1) Cb-645Cl-2-Indan H H 2-Nap Aa-1 BRA52 C 427 (M⁺ + 1) Cb-65 5Cl-2-Indan H H5-Ind Aa-2 BRA52 C 416 (M⁺ + 1) Cb-66 5Cl-2-Indan H H 1Me-5-1HIdz Aa-5BRA52 C 431 (M⁺ + 1) Cb-67 5Cl-2-Indan H H 3-Qu Aa-7 BRA52 C 428(M⁺ + 1) Cb-68 5Cl-2-Indan H H 1Et-5-1HIdz Aa-28 BRA52 C 445 (M⁺ + 1)Cb-69 4,7DCl-2-Indan H H 2-Nap Aa-1 BRA53 C 462 (M⁺ + 1) Cb-704,7DCl-2-Indan H H 5-Ind Aa-2 BRA53 C 451 (M⁺ + 1) Cb-71 4,7DCl-2-IndanH H 1Me-5-1HIdz Aa-5 BRA53 C 466 (M⁺ + 1) Cb-72 5,6DCl-2-Indan H H 2-NapAa-1 BRA54 C 462 (M⁺ + 1) Cb-73 5,6DCl-2-Indan H H 1Me-5-Ind Aa-3 BRA54C 465 (M⁺ + 1) Cb-74 5,6DCl-2-Indan H H 1Me-5-1HIdz Aa-5 BRA54 C 466(M⁺ + 1) Cb-75 5,6DCl-2-Indan H H 5-Bzt Aa-38 BRA54 C 469 (M⁺ + 1) Cb-765,6DCl-2-Indan H H 3-Qu Aa-7 BRA54 C 463 (M⁺ + 1) Cb-77 5,6DCl-2-Indan HH 1Et-5-1HIdz Aa-28 BRA54 C 480 (M⁺ + 1) Cb-78 4MeO-2-Indan H H 5-IndAa-2 BRA55 C 412 (M⁺ + 1) Cb-79 4MeO-2-Indan H H 5-1HIdz Aa-4 BRA55 C413 (M⁺ + 1) Cb-80 4MeO-2-Indan H H 1Me-5-1HIdz Aa-5 BRA55 C 427(M⁺ + 1) Cb-81 5MeO-2-Indan H H 2-Nap Aa-1 BRA56 C 423 (M⁺ + 1) Cb-825MeO-2-Indan H H 5-Ind Aa-2 BRA56 C 412 (M⁺ + 1) Cb-83 5MeO-2-Indan H H1Me-5-1HIdz Aa-5 BRA56 C 427 (M⁺ + 1) Cb-84 5MeO-2-Indan H H 5-Bzt Aa-38BRA56 C 430 (M⁺ + 1) Cb-90 5,6DMeO-2-Indan H H 2-Nap Aa-1 BRA57 C 453(M⁺ + 1) Cb-91 5,6DMeO-2-Indan H H 1Me-5-Ind Aa-3 BRA57 C 456 (M⁺ + 1)Cb-92 5,6DMeO-2-Indan H H 1Me-5-1HIdz Aa-5 BRA57 C 457 (M⁺ + 1) Cb-935,6DMeO-2-Indan H H 5-Bzt Aa-38 BRA57 C 460 (M⁺ + 1) Cb-945,6DMeO-2-Indan H H 3-Qu Aa-7 BRA57 C 454 (M⁺ + 1) Cb-955,6-DMeO-2-Indan H H 1Et-5-1HIdz Aa-28 BRA57 C 471 (M⁺ + 1) Cb-85 cHex HH 2-Nap Aa-1 BRA58 C 359 (M⁺ + 1) Cb-86 cHex H H 5-Ind Aa-2 BRA58 C 348(M⁺ + 1) Cb-87 cHex H H 1Me-5-Ind Aa-3 BRA58 C 362 (M⁺ + 1) Cb-88 cHex HH 5-1HIdz Aa-4 BRA58 C 349 (M⁺ + 1) Cb-89 cHex H H 1Me-5-1HIdz Aa-5BRA58 C 363 (M⁺ + 1)

Reference Examples Intermediate Ab-1 to Ab-47 Synthesis of methyl3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(naphthalen-2-yl)phenyl]propionate(Intermediate Ab-1)

Compound No. Aa-1 (253.2 mg), bispinacolate diboron (202.6 mg, Ald),PdCl₂(dppf) (43.4 mg) and potassium acetate (289 mg) were added to DMF(5.7 ml), and stirred with heating at 80° C. for 20 hours under argongas atmosphere. The reaction mixture was added with ethyl acetate (200ml), washed with saturated brine, and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=4:1) to obtain the titlecompound (Intermediate Ab-1, 194.6 mg).

Typical examples of the compounds of the present invention includingthose mentioned above that can be obtained by reacting and treatingcorresponding starting compounds according to the synthesis method ofIntermediate Ab-1 are shown in Table-Ab-1.

In the column indicated as “Mass” in the table, data of mass spectrameasured by fast atom bombardment mass spectrometry (FAB-MS) are shown.

TABLE Ab-1

Exp. AR Mass Ab-1 2-Nap 417 (M⁺ + 1) Ab-2 5-Ind 406 (M⁺ + 1) Ab-31Me-5-Ind 420 (M⁺ + 1) Ab-4 5-1HIdz 407 (M⁺ + 1) Ab-5 1Me-5-1HIdz 421(M⁺ + 1) Ab-6 5-BF 410 (M⁺ + 1) Ab-7 3-Qu 418 (M⁺ + 1) Ab-8 1-Nap 417(M⁺ + 1) Ab-9 6(MeO)-2-Nap 447 (M⁺ + 1) Ab-10 6(Me₂N)-2-Nap 460 (M⁺ + 1)Ab-11 4-Ind 406 (M⁺ + 1) Ab-12 1Me-4-Ind 420 (M⁺ + 1) Ab-13 6-Ind 406(M⁺ + 1) Ab-14 1Me-6-Ind 420 (M⁺ + 1) Ab-15 2-Ind 406 (M⁺ + 1) Ab-161Me-2-Ind 420 (M⁺ + 1) Ab-17 3-Ind 406 (M⁺ + 1) Ab-18 1Me-3-Ind 420(M⁺ + 1) Ab-19 1iPr-5-Ind 448 (M⁺ + 1) Ab-20 1cPen-5-Ind 474 (M⁺ + 1)Ab-21 3Me-5-Ind 420 (M⁺ + 1) Ab-22 1,3DMe-5Ind 434 (M⁺ + 1) Ab-231,2,3triMe-5Ind 448 (M⁺ + 1) Ab-24 4-1HIdz 407 (M⁺ + 1) Ab-251Me-4-1HIdz 421 (M⁺ + 1) Ab-26 5-1HIdz 407 (M⁺ + 1) Ab-27 1Me-5-1HIdz421 (M⁺ + 1) Ab-28 1Et-5-1HIdz 435 (M⁺ + 1) Ab-29 1Pr-5-1HIdz 449(M⁺ + 1) Ab-30 2Me-5-2HIdz 421 (M⁺ + 1) Ab-31 6-1HIdz 407 (M⁺ + 1) Ab-321Me-6-1HIdz 421 (M⁺ + 1) Ab-33 3Me-5-1HIdz 421 (M⁺ + 1) Ab-341,3DMe-5-1HIdz 435 (M⁺ + 1) Ab-35 5-BT 423 (M⁺ + 1) Ab-36 2,3DMe-5-BF435 (M⁺ + 1) Ab-37 5-2ABzt 439 (M⁺ + 1) Ab-38 5-Bzt 434 (M⁺ + 1) Ab-392Me-5-Bzt 438 (M⁺ + 1) Ab-40 2,2DMe-5-2ABzt 467 (M⁺ + 1) Ab-41 6-2ABzt439 (M⁺ + 1) Ab-42 6-Bzt 434 (M⁺ + 1) Ab-43 2Me-6-Bzt 438 (M⁺ + 1) Ab-446-Qu 418 (M⁺ + 1) Ab-45 6-IQ 418 (M⁺ + 1) Ab-46 2-BF 407 (M⁺ + 1) Ab-472-BT 423 (M⁺ + 1)

Example Da-1 Synthesis of methyl3-[4-(phenylmethyl)-3-(naphthalen-2-yl)phenyl]propionate (Compound No.Da-1)

According to a procedure described in literature (S. Chowdhury et al.,Tetrahedron. Lett., 1999, p. 7599), (Ph₃P)₄Pd (14.8 mg) and a solutionof benzyl bromide (corresponding to the substance mentioned in thecolumn of SM2 in Table-Da-1 mentioned later) in dimethoxyethane (1.3 ml)were stirred with heating at 50° C. for 10 minutes under argonatmosphere, then added with Compound Ab-1 (52.4 mg, corresponding to thesubstance mentioned in the column of SM1 in Table-Da-1 mentioned later),and 2 N sodium carbonate (160 μl), and refluxed by heating for 58 hours.The reaction mixture was added with ethyl acetate (60 ml), washedsuccessively with saturated aqueous sodium hydrogencarbonate andsaturated brine, dried, and then concentrated under reduced pressure.The residue was purified by flash column chromatography (hexane:ethylacetate=8:1) to obtain the title compound (Compound No. Da-1, 33.2 mg).

Example Da-2 Synthesis of3-[4-(phenylmethyl)-3-(naphthalen-2-yl)phenyl]propionic acid (CompoundNo. Da-2)

According to the procedure described in the synthesis method of CompoundCa-2 provided that the reaction was performed for 3 hours, Compound No.Da-1 (28.2 mg) and 2 N aqueous sodium hydroxide (38 μl) were reacted andtreated to obtain the title compound (Compound No. Da-2, 23.7 mg).

Examples Da-1 to Da-70

Typical examples of the compounds of the present invention includingthose mentioned in the examples described above, that can be obtained byreacting and treating corresponding starting compounds according to themethods described in Examples Da-1 and Da-2, are shown in Table-Da-1 andTable-Da-2.

The substances mentioned in the columns of “SM1” in the tablescorrespond to reaction intermediates, and those mentioned in the columnsof “SM2” in the tables correspond to the acid halide mentioned inExample Da-1. The halide reagents mentioned in the columns of “SM2” withthe symbols of “HAL (number))” are those mentioned in Table-Ha. Theregents for which cells of the columns of “Manufacturer” are blank inthe tables are synthesized according to a method described in ordinarychemical literature.

TABLE Ha Reagent Name of reagent Manufacturer HAL-1 Benzyl bromide AldHAL-2 4-Methoxybenzyl Ald bromide HAL-3 3-Methoxybenzyl Ald bromideHAL-4 2-Methoxybenzyl Ald bromide HAL-5 4-Methylbenzyl bromide Ald HAL-63-Methylbenzyl bromide Ald HAL-7 2-Methylbenzyl bromide Ald HAL-84-Trifluoromethylbenzyl Ald bromide HAL-9 3-Trifluoromethylbenzyl Aldbromide HAL-10 2-Trifluoromethylbenzyl Ald bromide HAL-11 4-Chlorobenzylbromide Ald HAL-12 3-Chlorobenzyl bromide Ald HAL-13 2-Chlorobenzylbromide Ald HAL-14 4-Fluorobenzyl bromide Ald HAL-15 3-Fluorobenzylbromide Ald HAL-16 2-Fluorobenzyl bromide Ald HAL-17 1-Bromo-2-phenylAld ethane HAL-18 1-Bromo-2-(4-chloro Ald phenyl)ethane HAL-191-Bromo-2-(3-chloro phenyl)ethane HAL-20 1-Bromo-2-(2-chlorophenyl)ethane HAL-21 1-Bromo-2-(4-dimethyl aminophenyl) ethane HAL-22Benzoyl chloride TCI HAL-23 Acetyl chloride WAKO HAL-24 i-Butyrylchloride Ald HAL-25 Cyclohexylcarbonyl Ald chloride HAL-264-Methoxybenzoyl TCI chloride HAL-27 4-Methylbenzoyl Ald chloride HAL-284-Chlorobenzoyl TCI chloride HAL-29 Phenylacetyl chloride WAKO HAL-302-Phenylpropionyl TCI chloride

TABLE Da-1

LCMS Exp. RxO Y Zx AR SM1 SM2 method RTime Mass Da-1 Ph Me H 2-Nap Ab-1HAL-1 D N.D Da-2 Ph H H 2-Nap Da-1 — C 367 (M⁺ + 1) Da-3 Ph Me H 5-IndAb-2 HAL-1 Da-4 Ph H H 5-Ind Da-3 — Da-5 Ph Me H 1Me-5-Ind Ab-3 Ha-1 C384 (M⁺ + 1) Da-6 Ph H H 1Me-5-Ind Da-5 — C 369 (M⁺ + 1) Da-7 Ph Me H5-1HIdz Ab-4 Ha-1 Da-8 Ph H H 5-1HIdz Da-7 — Da-9 Ph Me H 1Me-5-1HIdzAb-5 HAL-1 C 385 (M⁺ + 1) Da-10 Ph H H 1Me-5-1HIdz Da-9 — C 370 (M⁺ + 1)Da-11 4MeOPh H H 2-Nap Ab-1 HAL-2 Da-12 4MeOPh H H 5-Ind Ab-2 HAL-2Da-13 4MeOPh H H 1Me-5-1HIdz Ab-5 HAL-2 Da-14 3MeOPh H H 2-Nap Ab-1HAL-3 C 397 (M⁺ + 1) Da-15 3MeOPh H H 5-Ind Ab-2 HAL-3 Da-16 3MeOPh H H1Me-5-1HIdz Ab-5 HAL-3 Da-17 2MeOPh H H 2-Nap Ab-1 HAL-4 Da-18 2MeOPh HH 5-Ind Ab-2 HAL-4 Da-19 2MeOPh H H 1Me-5-1HIdz Ab-5 HAL-4 Da-20 4MePh HH 2-Nap Ab-1 HAL-5 C 381 (M⁺ + 1) Da-21 4MePh H H 5-Ind Ab-2 HAL-5 Da-224MePh H H 1Me-5-1HIdz Ab-5 HAL-5 Da-23 3MePh H H 2-Nap Ab-1 HAL-6 Da-243MePh H H 5-Ind Ab-2 HAL-6 Da-25 3MePh H H 1Me-5-1HIdz Ab-5 HAL-6 Da-262MePh H H 2-Nap Ab-1 HAl-7 C 381 (M⁺ + 1) Da-27 2MePh H H 5-Ind Ab-2HAl-7 C 370 (M⁺ + 1) Da-28 2MePh H H 1Me-5-1HIdz Ab-5 HAl-7 Da-29 4CF₃PhH H 2-Nap Ab-1 HAL-8 Da-30 4CF₃Ph H H 5-Ind Ab-2 HAL-8 Da-31 4CF₃Ph H H1Me-5-1HIdz Ab-5 HAL-8 Da-32 3CF₃Ph H H 2-Nap Ab-1 HAL-9 Da-33 3CF₃Ph HH 5-Ind Ab-2 HAL-9 Da-34 3CF₃Ph H H 1Me-5-1HIdz Ab-5 HAL-9 Da-35 2CF₃PhH H 2-Nap Ab-1 HAL-10 Da-36 2CF₃Ph H H 5-Ind Ab-2 HAL-10 Da-37 2CF₃Ph HH 1Me-5-1HIdz Ab-5 HAL-10 Da-38 4ClPh H H 2-Nap Ab-1 HAL-11 C 401(M⁺ + 1) Da-39 4ClPh H H 5-Ind Ab-2 HAL-11 C 390 (M⁺ + 1) Da-40 4ClPh HH 1Me-5-1HIdz Ab-5 HAL-11 Da-41 3ClPh H H 2-Nap Ab-1 HAL-12 Da-42 3ClPhH H 5-Ind Ab-2 HAL-12 Da-43 3ClPh H H 1Me-5-1HIdz Ab-5 HAL-12 Da-442ClPh H H 2-Nap Ab-1 HAL-13 Da-45 2ClPh H H 5-Ind Ab-2 HAL-13 Da-462ClPh H H 1Me-5-1HIdz Ab-5 HAL-13 De-47 4FPh H H 2-Nap Ab-1 HAL-14 C 385(M⁺ + 1) Da-48 4FPh H H 5-Ind Ab-2 HAL-14 Da-49 4FPh H H 1Me-5-1HIdzAb-5 HAL-14 C 389 (M⁺ + 1) Da-50 3FPh H H 2-Nap Ab-1 HAL-15

TABLE Da-2 LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Da-51 3FPh H H5-Ind Ab-2 HAL-15 Da-52 3FPh H H 1Me-5-1HIdz Ab-5 HAL-15 Da-53 2FPh H H2-Nap Ab-1 HAL-16 Da-54 2FPh H H 5-Ind Ab-2 HAL-16 Da-55 2FPh H H1Me-5-1HIdz Ab-5 HAL-16 Da-56 Bn H H 2-Nap Ab-1 HAL-17 C 381 (M⁺ + 1)Da-57 Bn H H 5-Ind Ab-2 HAL-17 Da-58 Bn H H 1Me-5-1HIdz Ab-5 HAL-17 C419 (M⁺ + 1) Da-59 4ClBn H H 2-Nap Ab-1 HAL-18 Da-60 4ClBn H H 5-IndAb-2 HAL-18 Da-61 4ClBn H H 1Me-5-1HIdz Ab-5 HAL-18 C 385 (M⁺ + 1) Da-623ClBn H H 2-Nap Ab-1 HAL-19 C 415 (M⁺ + 1) Da-63 3ClBn H H 5-Ind Ab-2HAL-19 Da-64 3ClBn H H 1Me-5-1HIdz Ab-5 HAL-19 Da-65 2ClBn H H 2-NapAb-1 HAL-20 Da-66 2ClBn H H 5-Ind Ab-2 HAL-20 Da-67 2ClBn H H1Me-5-1HIdz Ab-5 HAL-20 Da-68 4DMABn H H 2-Nap Ab-1 HAL-21 C 424(M⁺ + 1) Da-69 4DMABn H H 5-Ind Ab-2 HAL-21 C 413 (M⁺ + 1) Da-70 4DMABnH H 1Me-5-1HIdz Ab-5 HAL-21

Example Ea-1 Synthesis of methyl3-[4-(phenylcarbonyl)-3-(naphthalen-2-yl)phenyl]propionate (Compound No.Ea-1)

According to a procedure described in literature (Y. Urawa et al,Tetrahedron. Lett., 2003, p. 271), Compound Ab-1 (112.1 mg,corresponding to the substance mentioned in the column of SM1 inTable-Ea-1 mentioned later), dichlorobis(triphenylphosphine)palladium(18.9 mg, KANTO), and a solution of potassium phosphate (147.1 mg) intoluene (2.6 ml) were added with benzoyl chloride (47 μg, correspondingto the substance mentioned in the column of SM2 in Table-Ea-1), andstirred with heating at 110° C. for 48 hours under nitrogen atmosphere.The reaction mixture was washed successively with saturated aqueoussodium hydrogencarbonate, water and saturated brine, dried, and thenconcentrated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:ethyl acetate 7:1) to obtain the titlecompound (Compound No. Ea-1, 88.3 mg).

Example Ea-2 Synthesis of3-[4-phenylcarbonyl-3-(naphthalen-2-yl)phenyl]propionic acid (CompoundNo. Ea-2)

According to the procedure described in the synthesis method of CompoundCa-2 with the modification that the reaction was carried out for 3 hour,Compound No. Ea-1 (82.6 mg) and 2 N aqueous sodium hydroxide (105 ml)were reacted and treated to obtain the title compound (Compound No.Ea-2, 70.7 mg).

Examples Ea-1 to Ea-34

Typical examples of the compounds of the present invention includingthose mentioned in the examples described above, that can be obtained byreacting and treating corresponding starting compounds according to themethods described in Examples Ea-1 and Ea-2, are shown in Table-Ea-1.

The substances mentioned in the column of “SM1” in the table correspondto reaction intermediates, and those mentioned in the column of “SM2” inthe table correspond to acid chlorides mentioned in Table Ea-1. The acidchlorides mentioned with the symbols of “HAL (number)” in the column of“SM2” are those mentioned in Table-Ha.

TABLE Ea-1

LCMS Exp. Rx Y Zx AR SM1 SM2 method RTime Mass Ea-1 Ph Me H 2-Nap Ab-1HAL-22 C 395 (M⁺ + 1) Ea-2 Ph H H 2-Nap Ea-1 — C 381 (M⁺ + 1) Ea-3 Ph MeH 5-Ind Ab-2 HAL-22 Ee-4 Ph H H 5-Ind Ea-3 — Ea-5 Ph Me H 1Me-5-Ind Ab-3HAL-22 C 398 (M⁺ + 1) Ea-6 Ph H H 1Me-5-Ind Ea-5 — C 384 (M⁺ + 1) Ea-7Ph Me H 5-1HIdz Ab-4 HAL-22 Ea-8 Ph H H 5-1HIdz Ea-7 — Ea-9 Ph Me H1Me-5-1HIdz Ab-5 HAL-22 C 399 (M⁺ + 1) Ea-10 Ph H H 1Me-5-1HIdz Ea-9 — C385 (M⁺ + 1) Ea-11 Me H H 2-Nap Ab-1 HAL-23 C 319 (M⁺ + 1) Ea-12 Me H H5-Ind Ab-2 HAL-23 C 308 (M⁺ + 1) Ea-13 Me H H 1Me-5-1HIdz Ab-5 HAL-23Ea-14 iBu H H 2-Nap Ab-1 HAL-24 C 361 (M⁺ + 1) Ea-15 iBu H H 5-Ind Ab-2HAL-24 Ea-16 iBu H H 1Me-5-1HIdz Ab-5 HAL-24 C 365 (M⁺ + 1) Ea-17 cHex HH 2-Nap Ab-1 HAL-25 C 386 (M⁺ + 1) Ea-18 cHex H H 5-Ind Ab-2 HAL-25Ea-19 cHex H H 1Me-5-1HIdz Ab-5 HAL-25 Ea-20 4MeOPh H H 2-Nap Ab-1HAL-26 C 411 (M⁺ + 1) Ea-21 4MeOPh H H 5-Ind Ab-2 HAL-26 C 400 (M⁺ + 1)Ea-22 4MeOPh H H 1Me-5-1HIdz Ab-5 HAL-26 Ea-23 4MePh H H 2-Nap Ab-1HAL-27 Ea-24 4MePh H H 5-Ind Ab-2 HAL-27 Ea-25 4MePh H H 1Me-5-1HIdzAb-5 HAL-27 Ea-26 4ClPh H H 2-Nap Ab-1 HAL-28 C 415 (M⁺ + 1) Ea-27 4ClPhH H 5-Ind Ab-2 HAL-28 Ea-28 4ClPh H H 1Me-5-1HIdz Ab-5 HAL-28 Ea-29 Bn HH 2-Nap Ab-1 HAL-29 C 395 (M⁺ + 1) Ea-30 Bn H H 5-Ind Ab-2 HAL-29 Ea-31Bn H H 1Me-5-1HIdz Ab-5 HAL-29 C 399 (M⁺ + 1) Ea-32 1PhEt H H 2-Nap Ab-1HAL-30 C 409 (M⁺ + 1) Ea-33 1PhEt H H 5-Ind Ab-2 HAL-30 C 398 (M⁺ + 1)Ea-34 1PhEt H H 1Me-5-1HIdz Ab-5 HAL-30

Reference Examples Intermediate Ac-1 and Ac-2 Synthesis oft-butyldimethylsilyl3-[3-bromo-4-(t-butyldimethylsilyloxy)phenyl]acrylate (IntermediateAc-1)

According to the procedure described in the synthesis method ofIntermediate 43, 3-[3-bromo-4-hydroxylphenyl]acrylic acid (12.01 g)obtainable from 4-hydroxybenzaldehyde (TCI) by a method known fromliterature (Y. Nagao et al., Tetrahedron Lett., 1980, p. 4931) wasreacted with imidazole (16.01 g) and t-butyldimethylsilyl chloride (7.43g) and treated to obtain the title compound (Intermediate Ac-1, 17.43g).

Synthesis of 3-[3-bromo-4-(t-butyldimethylsilyloxy)phenyl]acrylic acid(Intermediate Ac-2)

A solution of Compound Ac-1 (17.43 g) in methanol (100 ml) was addedwith 1 N hydrochloric acid (5 ml), and stirred at room temperature for 3hours. The reaction solution was extracted with ethyl acetate (500 ml),and washed with saturated brine. The organic layer was dried, and thenthe solvent was evaporated under reduced pressure. The residue waspurified by flash column chromatography (hexane:ethyl acetate=6:1) toobtain the title compound (Compound No. Ac-2, 14.60 g).

Example Ga-1 Synthesis of methyl3-[3-(1H-indol-5-yl)-4-(3-pyridinemethyloxy)phenyl]acrylate (CompoundNo. Ga-1) (Step 1)

A solution of Compound Ac-2 (3.06 g), diisopropyl carbodiimide(henceforth abbreviated as “DIC”, 1.33 ml) and dimethylaminopyridine(86.8 mg) in DMF (100 ml) was added with SynPhase-PS-D-series Lantern,Hydroxymethylphenoxy Linker (henceforth abbreviated as “PSL”, 0.035 mmolper lantern, 81 lanterns, Mimotopes), and left standing at roomtemperature for 16 hours. After the reaction mixture was removed, PSLwas washed successively with DMF (100 ml), methanol (100 ml),dichloromethane (100 ml), and THF (100 ml) three times for each, anddried under reduced pressure.

PSL (81 lanterns mentioned above) was added to a solution oftetrabutylammonium fluoride (8.5 ml, Ald, 1 N THF solution) in THF (80ml), and left standing at room temperature for 23 hours. After thereaction mixture was removed, PSL was successively washed with DMF (100ml) three times, alternately with DMF:water:acetic acid (75:25:1, 100ml) and methanol:water:acetic acid (75:25:1, 100 ml) twice for each,alternately with DMF:water (4:1, 100 ml) and methanol:water (4:1, 100ml) twice for each, and with THF (100 ml), chloroform (100 ml), DMF (100ml), and chloroform (100 ml) twice for each, and then dried underreduced pressure to obtain PLS-1 (81 lanterns).

(Step 2)

SL-1 (3 lanterns out of those mentioned above) was added to a mixedsolution of 3-pyridinemethanol (147.6 μl, corresponding to the substancementioned in the column of SM1 in Table-Ga-1 mentioned later), DBAB(242.1 mg, Sigma) and Ph₃P (275.6 mg, KANTO) in dehydrated THF (3.24ml), and left standing at room temperature for 15 hours. After thereaction mixture was removed, PSL was successively washed with THF (3.5ml) and DMF (3.5 ml) four times for each, alternately with methanol (3.5ml) and DMF (3.5 ml) twice for each, alternately with DMF (3.5 ml) anddichloromethane (3.5 ml) twice for each, with dichloromethane (3.5 ml)twice, and dried under reduced pressure to obtain PSL-2 (3 vials).

(Step 3)

SL-2 (1 lantern out of those mentioned above) was added to a mixedsolution of 1H-indole-5-boronic acid (11.3 mg, corresponding to thesubstance mentioned in the column of SM2 in Table-Ga-1 mentioned later),(Ph₃P)₄Pd (8.1 mg), and 2 N aqueous cesium carbonate (176 μl) in DMF(800 μl), and heated at 80° C. for 18 hours under argon atmosphere.After the reaction mixture was removed, PSL was successively washed withDMF (1.0 ml) four times, with methanol (1.0 ml) twice, alternately withDMF (1.0 ml) and methanol (1.0 ml) twice for each, alternately with DMF(1.0 ml) and dichloromethane (1.0 ml) twice for each, and withdichloromethane (1.0 ml) twice, and dried under reduced pressure. ThisPSL was added to a solution of sodium methoxide (175 μl, WAKO, 1 Nsolution in methanol) in THF:methanol (2:1, 1.5 ml), and left standingat room temperature for 19 hours. After the reaction, PSL was removed,and the reaction solution was added with water (500 μl), and stirredwith heating at 60° C. for 3 hours. The reaction solution wasconcentrated under reduced pressure, then added with water (200 μl) andchloroform (1 ml), and passed through a diatomaceous earth column, andthe obtained filtrate was concentrated under reduced pressure to obtainthe title compound (Compound No. Ga-1, 10.6 mg).

Examples Ga-1 to Ga-55

Typical examples of the compounds of the present invention includingthose mentioned in the examples described above, that can be obtained byreacting and treating corresponding starting compounds according to themethod described in Example Ga-1, are shown in Table-Ga-1 andTable-Ga-2.

The substances mentioned in the columns of “SM1” in the tablescorrespond to the alcohol reagent mentioned in Example Ga-1, and thosementioned in the columns of “SM2” in the tables correspond to theboronic acid reagent mentioned in Table Ga-1. The alcohol reagentsmentioned in the columns of “SM1” with the symbols of “ALC (number))”are those mentioned in Table-I. The boronic acid reagents mentioned withthe symbols of “BRA (number))” in the columns of “SM2” are thosementioned in Table-Ba-1 and Table-Ba-2.

TABLE I Reagent Name of reagent Manufacture ALC-1 Cyclopentanol KANTOALC-2 Cyclohexanol Ald ALC-3 Benzyl Alcohol Ald ALC-4 2-Methyl-1-propylalcohol TCI ALC-5 4-Fluorophenetyl Ald alcohol ALC-6 1-PhenylethanolWAKO ALC-7 2-(N-Methylanilino)ethanol TCI ALC-8 2-Hydroxy indane TCIALC-9 2-Hydroxymethyl- TCI 1,4-benzodioxane ALC-102-(4-Dimethyl)phenylethanol Ald ALC-11 3-Pyridine methanol TCI ALC-12m-Chlorobenzyl alcohol TCI ALC-13 4-n-Butoxybenzyl alcohol TCI ALC-142-Hydroxyacetophenone TCI ALC-15 2-Phenoxy ethanol TCI ALC-162-Phenylthio ethanol TCI ALC-17 5-(2-Hydroxyethyl)- TCI 4-methylthiazolALC-18 1-Butanol TCI ALC-19 2-Hydroxyethyl acetate TCI ALC-20N-(2-Hydroxyethyl)morpholine TCI ALC-21 2-(2- TCI Dimethylaminoethoxy)ALC-22 Methyl glycolate TCI ALC-23 1-Phenyl ethanol TCI ALC-242-Chlorobenzyl alcohol TCI ALC-25 3-Chlorobenzyl alcohol TCI ALC-264-Chlorobenzyl alcohol TCI ALC-27 2-Methoxybenzyl TCI alcohol ALC-283-Methoxybenzyl TCI alcohol ALC-29 4-Methoxybenzyl TCI alcohol

TABLE Ga-1

LCMS Exp. RxO Y Zx AR SM1 SM2 method RTime Mass Ga-1 3PyMeO H H 5-IndALC-11 BRA2 A 3.27 371 (M⁺ + 1) Ga-2 2(PhS)EtO H H 5-Ind ALC-16 BRA2Ga-3

H H 5-Ind ALC-17 BRA2 A 3.07 405 (M⁺ + 1) Ga-4 nBuO H H 5-Ind ALC-18BRA2 Ga-5

H H 5-Ind ALC-21 BRA2 Ga-6 cPenO H H 5-Ind ALC-1 BRA2 Ga-7 cHexO H H5-Ind ALC-2 BRA2 Ga-8 PhMeO H H 5-Ind ALC-3 BRA2 A 3.79 356 (M⁺ + 1)Ga-9 cPenO H H 2-BF ALC-1 BRA18 Ga-10 cHexO H H 2-BF ALC-2 BRA18 Ga-112-IndanO H H 2-BF ALC-8 BRA18 A 3.85 397 (M⁺ + 1) Ga-12 3PyMeO H H 2-BFALC-11 BRA18 Ga-13 2(PhS)EtO H H 2-BF ALC-16 BRA18 A 3.61 417 (M⁺ + 1)Ga-14

H H 2-BF ALC-17 BRA18 Ga-15 nBuO H H 2-BF ALC-18 BRA18 Ga-16

H H 2-BF ALC-21 BRA18 Ga-17 cPenO H H 1Me-5-1HIdz ALC-1 BRA6 Ga-18 cHexOH H 1Me-5-1HIdz ALC-2 BRA6 A 3.74 377 (M⁺ + 1) Ga-19 2-IndanO H H1Me-5-1HIdz ALC-8 BRA6 Ga-20 3PyMeO H H 1Me-5-1HIdz ALC-11 BRA6 Ga-212(PhS)EtO H H 1Me-5-1HIdz ALC-16 BRA6 Ga-22

H H 1Me-5-1HIdz ALC-17 BRA6 Ga-23 nBuO H H 1Me-5-1HIdz ALC-18 BRA6 Ga-24

H H 1Me-5-1HIdz ALC-21 BRA6 Ga-25 3PyMeO H H 1-Nap ALC-11 BRA16 Ga-262(PhS)EtO H H 1-Nap ALC-16 BRA16 C 427 (M⁺ + 1) Ga-27

H H 1-Nap ALC-17 BRA16 Ga-28 nBuO H H 1-Nap ALC-18 BRA16 Ga-29

H H 1-Nap ALC-21 BRA16 Ga-30 1PhEtO H H 5-Ind ALC-6 BRA2

TABLE Ga-2 LCMS Exp. RxO Y Zx AR SM1 SM2 method RTime Mass Ga-31 1PhEtOH H 2-BF ALC-6 BRA18 Ga-32 1PhEtO H H 1Me-5-1HIdz ALC-6 BRA6 A 3.55 399(M⁺ + 1) Ga-33 1PhEtO H H 1-Nap ALC-6 BRA16 Ga-34 1PhEtO H H 2-Nap ALC-6BRA1 Ga-35 1PhEtO H H 2-Nap ALC-6 BRA1 C 395 (M⁺ + 1) Ga-36 1PhEtO H H5-Ind ALC-6 BRA2 Ga-37 2ClPhMeO H H 2-Nap ALC-24 BRA1 Ga-38 2ClPhMeO H H5-Ind ALC-24 BRA2 Ga-39 3ClPhMeO H H 2-Nap ALC-25 BRA1 C 415 (M⁺ + 1)Ga-40 3ClPhMeO H H 5-Ind ALC-25 BRA2 Ga-41 4ClPhMeO H H 2-Nap ALC-26BRA1 Ga-42 4ClPhMeO H H 5-Ind ALC-26 BRA2 C 404 (M⁺ + 1) Ga-43 2MeOPhMeOH H 2-Nap ALC-27 BRA1 Ga-44 2MeOPhMeO H H 5-Ind ALC-27 BRA2 Ga-453MeOPhMeO H H 2-Nap ALC-28 BRA1 Ga-46 3MeOPhMeO H H 5-Ind ALC-28 BRA2Ga-47 4MeOPhMeO H H 2-Nap ALC-29 BRA1 Ga-48 4MeOPhMeO H H 5-Ind ALC-29BRA2 Ga-49 nBuO H H 3-Qu ALC-18 BRA10 C 348 (M⁺ + 1) Ga-50 nBuO H H3-Thienyl ALC-18 BRA36 Ga-51 nBuO H H 4-Py ALC-18 BRA26 Ga-52 nBuO H HcPen ALC-18 BRA28 Ga-53 nBuO H H 2FPh ALC-18 BRA32 C 315 (M⁺ + 1) Ga-54nBuO H H 3FPh ALC-18 BRA33 Ga-55 nBuO H H 4FPh ALC-18 BRA34

Reference Examples Intermediate s-1 to s-52 Synthesis of methyl3-[4-(4-methylphenylthio)-3-nitrophenyl]acrylate (Intermediate s-1)(Synthesis method SF)

A solution of 3-[4-(4-methylphenylthio)-3-nitrophenyl]acrylic acid (631mg, MAYB) in a mixture of methanol (12.6 ml), ethyl acetate (6.3 ml) andTHF (6.3 ml) was added dropwise to methanol (12.6 ml) beforehand underice cooling, and then the mixture was added with a solution of thionylchloride (735 μl, KANTO) in methanol (50 ml) under ice cooling, stirredfor 30 minutes, then warmed to room temperature, and further stirred for15.5 hours. The reaction mixture was poured into aqueous sodiumhydrogencarbonate (50 ml) for neutralization, and extracted with ethylacetate (50 ml), and the organic layer was washed with saturated brine.The organic layer was dried, and then the solvent was evaporated underreduced pressure to obtain the title compound (Intermediate s-1, 659mg).

Synthesis of methyl 3-[4-(4-methylphenylthio)-3-nitrophenyl]propionate(Intermediate s-2) (Synthesis method SDI)

A solution of Intermediate s-1 (494 mg) in ethyl acetate (75 ml) wasadded with 10% palladium hydroxide/carbon (150 mg, NE CHEMCAT), andstirred at room temperature for 14 hours under hydrogen atmosphere. Thereaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure. The residue was dissolved in methanol(75 ml) again, added with 5 N hydrochloric acid (600 μl) and 10%palladium hydroxide/carbon (151 mg), and stirred at room temperature for22 hours under hydrogen atmosphere. The reaction mixture was filtered,and the solvent of the filtrate was evaporated under reduced pressure toobtain the title compound (Intermediate s-2, 419 mg).

Synthesis of methyl 3-[3-bromo-4-(4-methylphenylthio)phenyl]propionate(Intermediate s-3) (Synthesis method SE1)

A solution of hydrobromic acid (690 μl) in methanol (3.2 ml) was addedwith a solution of Intermediate s-2 (362 mg) in methanol (3.2 ml) underice cooling. This mixture was added dropwise with an aqueous solution(320 μl) of sodium nitrite (84 mg, WAKO).

An aqueous solution (3.2 ml) of copper(II) bromide (270 mg, WAKO) washeated to 40° C. added dropwise with the previously obtained solutionover 20 minutes, and stirred at the same temperature for 1.5 hours.

The reaction mixture was extracted with ethyl acetate (40 ml). Theorganic layer was washed successively with water and saturated brine,and dried, and then the solvent was evaporated under reduced pressure.The residue was purified by flash column chromatography (hexane:ethylacetate=9:1) to obtain the title compound (Intermediate s-3, 167 mg).

Synthesis of methyl 3-(3-bromo-4-fluorophenyl)acrylate (Intermediates-4) (Synthesis method SF)

According to the procedure described in the synthesis method ofIntermediate n−1 (Synthesis method SF) provided that the reaction wasperformed for 1 hour, 3-bromo-4-fluorocinnamic acid (3.30 g, LANC) andthionyl chloride (1.5 ml, WAKO) were reacted and treated to obtain thetitle compound (Intermediate n-25, 3.47 g).

Synthesis of methyl 3-[3-bromo-4-(4-methoxyphenylthio)phenyl]acrylate(Intermediate s-5) (Synthesis method SC)

A solution of Intermediate s-4 (259.1 mg) in DMSO (4 ml) was added withpotassium carbonate (156.9 mg) and p-methoxythiophenol (148 μl, TCI),and stirred at 70° C. for 16 hours. The reaction mixture was extractedwith ethyl acetate (30 ml), and then the organic layer was washedsuccessively with water and saturated brine, and dried. Then, thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=8:1) to obtain thetitle compound (Intermediate s-5, 283.3 mg).

Synthesis of methyl 3-[3-bromo-4-(4-methoxyphenylthio)phenyl)propionate(Intermediate s-6) (Synthesis method SD2)

According to a procedure described in literature [D. J. Hart et al.,Journal of Organic Chemistry (J. Org. Chem.), 1987, vol. 52, p. 4665], asolution of Intermediate s-5 (579.1 mg) in dimethoxyethane (40 ml) wasadded with p-toluenesulfonhydrazide (1.99 g, TCI), and refluxed byheating at 110° C. Then, the reaction mixture was added dropwise with anaqueous solution (40 ml) of sodium acetate (1.54 g, WAKO) over 1 hour,and further stirred for 3 hours. The reaction mixture was extracted withdichloromethane (150 ml), and the organic layer was washed with water,and dried. Then, the solvent was evaporated under reduced pressure. Theresidue was purified by column chromatography (Quad, hexane:ethylacetate=7:1) to obtain the title compound (Intermediate s-6, 583.5 mg).

Synthesis of 3-bromo-4-(cyclopentylthio)benzaldehyde (Intermediate s-23)(Synthesis method SC)

A solution of 3-bromo-4-fluorobenzaldehyde (517.4 mg) in DMSO (8 ml) wasadded with potassium carbonate (514.9 mg) and cyclopentanethiol (250 μl,TCI), and stirred at 90° C. for 17 hours. The reaction mixture wasextracted with ethyl acetate (50 ml), and the organic layer was washedsuccessively with water and saturated brine, and dried. Then, thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=8:1) to obtain thetitle compound (Intermediate S-23, 644.7 mg).

Synthesis of ethyl 3-[3-bromo-4-(cyclopentylthio)phenyl]acrylate(Intermediate s-24) (Synthesis method SE2)

A solution of Intermediate s-23 (243.7 mg) in 1,2-dimethoxyethane (8 ml)was added with ethyl diethylphosphonoacetate (300 μl, TCI), and addedwith 60% sodium hydride (49.8 mg) under ice cooling. The reactionmixture was stirred for 10 minutes, then warmed to room temperature, andstirred for 1 hour. The reaction mixture was added with water (5 ml) forquenching, added with dichloromethane (30 ml) for extraction, and washedwith saturated brine. The organic layer was dried, and then the solventwas evaporated under reduced pressure. The residue was purified bycolumn chromatography (Quad, hexane:ethyl acetate=4:1) to obtain thetitle compound (Intermediate s-24, 286.2 mg).

Typical examples of the intermediates including those mentioned abovethat can be obtained by reacting and treating corresponding startingcompounds using any of the methods described in the presentspecification are shown in Table-Int. S-1 and Table-Int. S-2. In thetables, intermediate numbers are mentioned in the columns indicated as“Exp”. In the tables, used methods among those described above arementioned in the columns of “Syn” with symbols, the starting compounds 1are mentioned in the columns of “SM1”, and the starting compounds 2 arementioned in the columns of “SM2”. Further, the compounds indicated as“Single” in the columns of “Single or Double” in Table-Int.S-1 arecompounds in which two of the carbon atoms binding the benzene ring andcarbonyl group in the compounds are bound with a single bond, and thoseindicated as “Double” in the same are compounds in which two of thecarbon atoms binding the benzene ring and carbonyl group in thecompounds are bound with a double bond.

TABLE Ga-1

Single or LCMS Exp. Syn. SM1 SM2 Rx—S Y Double method RTime Mass Int.s-5SC Int.s-4 4MeOPhSH 4MeOPhS Me Double D 5.87 378 (M⁺ + 1) Int.s-6 SD2Int.s-5 4MeOPhS Me Single C 380 (M⁺ + 1) Int.s-7 SC Int.s-4 2MeOPhSH2MeOPhS Me Double C 378 (M⁺ + 1) Int.s-8 SD2 Int.s-7 2MeOPhS Me Single C380 (M⁺ + 1) Int.s-9 SC Int.s-4 3MeOPhSH 3MeOPhS Me Double C 378(M⁺ + 1) Int.s-10 SD2 Int.s-9 3MeOPhS Me Single C 380 (M⁺ + 1) Int.s-11SC Int.s-4 2MePhSH 2MePhS Me Double C 368 (M⁺ + 1) Int.s-12 SD2 Int.s-112MePhS Me Single D 5.70 N.D Int.s-13 SC Int.s-4 3MePhSH 3MePhS Me DoubleC 368 (M⁺ + 1) Int.s-14 SD2 Int.s-13 3MePhS Me Single C 366 (M⁺ + 1)Int.s-15 SC Int.s-4 4MePhSH 4MePhS Me Double C 368(M⁺ + 1) Int.s-16 SD2Int.s-15 4MePhS Me Single C 366 (M⁺ + 1) Int.s-17 SC Int.s-4 2FPhSH2FPhSMe Me Double C 368 (M⁺ + 1) Int.s-18 SD2 Int.s-17 2FPhS Me Single C370 (M⁺ + 1) Int.s-19 SC Int.s-4 3FPhSH 3FPhS Me Double C 368 (M⁺ + 1)Int.s-20 SD2 Int.s-19 3FPhS Me Single C 370 (M⁺ + 1) Int.s-21 SC Int.s-44FPhSH 4FPhS Me Double C 368 (M⁺ + 1) Int.s-22 SD2 Int.s-21 4FPhS MeSingle C 370 (M⁺ + 1) Int.s-24 SE2 Int.s-23 cPenS Me Double D 6.35 340(M⁺ + 1) Int.s-25 SD2 Int.s-24 cPenS Me Single C 342 (M⁺ + 1) Int.s-27SE2 Int.s-26 cHexS Et Double C 354 (M⁺ + 1) Int.s-28 SD2 Int.s-27 cHexSEt Single C 356 (M⁺ + 1) Int.s-30 SE2 Int.s-29 nPrS Et Double C 328(M⁺ + 1) Int.s-31 SD2 Int.s-30 nPrS Et Single C 330 (M⁺ + 1) Int.s-33SE2 Int.s-32 iPrS Et Double C 328 (M⁺ + 1) Int.s-34 SD2 Int.s-33 iPrS EtSingle C 330 (M⁺ + 1) Int.s-36 SE2 Int.s-35 nBuS Et Double C 328(M⁺ + 1) Int.s-37 SD2 Int.s-36 nBuS Et Single C 330 (M⁺ + 1) Int.s-39SE2 Int.s-38 iBuS Me Double D 5.86 330 (M⁺ + 1) Int.s-40 SD2 Int.s-39iBuS Me Single D 6.23 330 (M⁺ + 1) Int.s-42 SE2 Int.s-41 2PhEtS MeDouble D 6.18 376 (M⁺) Int.s-43 SD2 Int.s-42 2PhEtS Me Single D 6.21 378(M⁺) Int.s-45 SE2 Int.s-44 4MeOBnS Et Double C 393 (M⁺ + 1) Int.s-46 SD2Int.s-45 4MeOBnS Et Single C 395 (M⁺ + 1) Int.s-48 SE2 Int.s-47 4FBnS EtDouble C 381 (M⁺ + 1) Int.s-49 SD2 Int.s-48 4FBnS Et Single C 383(M⁺ + 1) Int.s-51 SE2 Int.s-50 2MeBnS Et Double C 377 (M⁺ + 1) Int.s-52SD2 Int.s-51 2MeBnS Et Single C 379 (M⁺ + 1)

TABLE Int.S-2

LCMS Exp. Syn. SM1 SM2 Rx—S method RTime Mass Int.s-23 SC cPenSH cPenS C286 (M⁺ + 1) Int.s-26 SC cHexSH cHexS C 300 (M⁺ + 1) Int.s-29 SC nPrSHnPrS C 260 (M⁺ + 1) Int.s-32 SC iPrSH iPrS C 260 (M⁺ + 1) Int.s-35 SCnBuSH nBuS C 274 (M⁺ + 1) Int.s-38 SC iBuSH iBuS C 274 (M⁺ + 1) Int.s-41SC 2PhEtSH 2PhEtS C 322 (M⁺ + 1) Int.s-44 SC 4MeOBnSH 4MeOBnS C 322(M⁺ + 1) Int.s-47 SC 4FBnSH 4FBnS C 326 (M⁺ + 1) Int.s-50 SC 2MeBnSH2MeBnS C 322 (M⁺ + 1)

Example S-a-1 Synthesis of methyl3-[3-(naphthalen-2-yl)-4-(4-methylphenylthio)phenyl]propionate (CompoundNo. N-a-1) (Synthesis method SB)

A solution of Intermediate s-3 (146 mg) in toluene (2 ml) was added with2-naphthaleneboronic acid (132.3 mg, TCI), 2 M aqueous sodium carbonate(600 μml), methanol (500 μl), and tetrakistriphenylphosphinepalladium(0) (henceforth abbreviated as “(Ph₃P)₄Pd”, 38 mg, NacalaiTesque), and stirred at 80° C. for 14.5 hours. The reaction mixture wasadded with ethyl acetate (40 ml), and washed successively with saturatedaqueous sodium hydrogencarbonate, saturated aqueous ammonium chlorideand saturated brine. The organic layer was dried, and then the solventwas evaporated under reduced pressure. The residue was purified by flashcolumn chromatography (hexane:ethyl acetate 4:1) to obtain the titlecompound (Compound No. S-a-1, 78 mg).

Example S-a-2 Synthesis of3-[3-(naphthalen-2-yl)-4-(4-methylphenylthio)phenyl]propionic acid(Compound No. S-a-2) (Synthesis method SA)

A solution of the compound of Example S-a-1 (51 mg) in methanol (5.0 ml)was added with 2 N aqueous sodium hydroxide (130 μl), and stirred at 60°C. for 2 hours. The reaction mixture was concentrated under reducedpressure, then made acidic with 5% aqueous hydrochloric acid under icecooling, and then extracted with ethyl acetate (30 ml). The organiclayer was washed with saturated brine, and dried, and then the solventwas evaporated under reduced pressure to obtain the title compound(Compound No. S-a-2, 47 mg).

Example S-c-1 Synthesis of methyl3-[4-(4-methoxyphenylthio)-3-(naphthalen-2-yl)phenyl]propionate(Compound No. S-c-1) (Synthesis method SD2)

According to the procedure described in the synthesis method ofIntermediate s-6 (Synthesis method), the compound of Example S-b-1 (3.01g), p-toluenesulfonhydrazide (430.1 mg), and sodium acetate (380.4 mg)were reacted and treated to obtain the title compound (Compound No.S-c-1, 95.1 mg).

Examples S-a-1 to S-a-24, S-b-1 to S-b-138 and S-c-1 to S-c-138

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-S-A-1, Table-S-B-1 toTable-S-B-3 and Table-S-C-1 to Table-S-C-3. In the tables, the compoundnumbers are mentioned in the columns indicated as “Exp.”. In the tables,used methods among the aforementioned synthesis methods are shown in thecolumns of “Syn” with symbols, the starting compounds 1 are mentioned inthe columns of “SM1”, and the starting compounds 2 are mentioned in thecolumns of “SM2”. The boronic acid reagents shown with the symbols of“BRA (number)” in the columns of “SM2” are those mentioned in Table-Ba-1and Table-Ba-2.

TABLE S-A-1

LCMS Exp. Syn SM1 SM2 Rx Y AR method RTime Mass S-a-1 SB Int.s-3 BRA14MePh Me 2-Nap C 413 (M⁺ + 1) S-a-2 SA S-a-1 4MePh H 2-Nap C 399(M⁺ + 1) S-a-3 SB Int.s-3 BRA2 4MePh Me 5-Ind C 402 (M⁺ + 1) S-a-4 SAS-a-3 4MePh H 5-Ind C 388 (M⁺ + 1) S-a-5 SB Int.s-3 BRA3 4MePh Me1Me-5-Ind C 416 (M⁺ + 1) S-a-6 SA S-a-5 4MePh H 1Me-5-Ind C 402 (M⁺ + 1)S-a-7 SB Int.s-3 BRA4 4MePh Me 1Et-5-Ind C 430 (M⁺ + 1) S-a-8 SA S-a-74MePh H 1Et-5-Ind C 416 (M⁺ + 1) S-a-9 SB Int.s-3 BRA5 4MePh Me 5-1HIdzC 403 (M⁺ + 1) S-a-10 SA S-a-9 4MePh H 5-1HIdz C 389 (M⁺ + 1) S-a-11 SBInt.s-3 BRA6 4MePh Me 1Me-5-1HIdz C 417 (M⁺ + 1) S-a-12 SA S-a-11 4MePhH 1Me-5-1HIdz C 403 (M⁺ + 1) S-a-13 SB Int.s-3 BRA7 4MePh Me 1Et-5-1HIdzC 431 (M⁺ + 1) S-a-14 SA S-a-13 4MePh H 1Et-5-1HIdz C 417 (M⁺ + 1)S-a-15 SB Int.s-3 BRA8 4MePh Me 2Me-5-2HIdz C 417 (M⁺ + 1) S-a-16 SAS-a-15 4MePh H 2Me-5-2HIdz C 403 (M⁺ + 1) S-a-17 SB Int.s-3 BRA9 4MePhMe 5-Bzt C 420 (M⁺ + 1) S-a-18 SA S-a-17 4MePh H 5-Bzt C 406 (M⁺ + 1)S-a-19 SB Int.s-3 BRA10 4MePh Me 3-Qu C 414 (M⁺ + 1) S-a-20 SA S-a-194MePh H 3-Qu C 400 (M⁺ + 1) S-a-21 SB Int.s-3 BRA11 4MePh Me 6-Qu C 414(M⁺ + 1) S-a-22 SA S-a-21 4MePh H 6-Qu C 400 (M⁺ + 1) S-a-23 SB Int.s-3BRA12 4MePh Me 6-IQ C 414 (M⁺ + 1) S-a-24 SA N-a-23 4MePh H 6-IQ C 400(M⁺ + 1)

TABLE S-B-1

LCMS Exp. Syn SM1 SM2 Rx Y AR method RTime Mass S-b-1 SB Int.s-5 BRA14MeOPh Me 2-Nap C 427 (M⁺ + 1) S-b-2 SA S-b-1 4MeOPh H 2-Nap C 413(M⁺ + 1) S-b-3 SB Int.s-5 BRA2 4MeOPh Me 5-Ind C 416 (M⁺ + 1) S-b-4 SAS-b-3 4MeOPh H 5-Ind C 402 (M⁺ + 1) S-b-5 SB Int.s-5 BRA3 4MeOPh Me1Me-5-Ind C 430 (M⁺ + 1) S-b-6 SA S-b-5 4MeOPh H 1Me-5-Ind C 416(M⁺ + 1) S-b-7 SB Int.s-5 BRA4 4MeOPh Me 1Et-5-Ind C 444 (M⁺ + 1) S-b-8SA S-b-7 4MeOPh H 1Et-5-Ind C 430 (M⁺ + 1) S-b-9 SB Int.s-5 BRA5 4MeOPhMe 5-1HIdz C 417 (M⁺ + 1) S-b-10 AS S-b-9 4MeOPh H 5-1HIdz C 403(M⁺ + 1) S-b-11 SB Int.s-5 BRA6 4MeOPh Me 1Me-5-1HIdz C 431 (M⁺ + 1)S-b-12 SA S-b-11 4MeOPh H 1Me-5-1HIdz C 417 (M⁺ + 1) S-b-13 SB Int.s-5BRA7 4MeOPh Me 1Et-5-1HIdz C 445 (M⁺ + 1) S-b-14 SA S-b-13 4MeOPh H1Et-5-1HIdz C 431 (M⁺ + 1) S-b-15 SB Int.s-5 BRA8 4MeOPh Me 2Me-5-2HIdzC 431 (M⁺ + 1) S-b-16 SA S-b-15 4MeOPh H 2Me-5-2HIdz C 417 (M⁺ + 1)S-b-17 SB Int.s-5 BRA9 4MeOPh Me 5-Bzt C 434 (M⁺ + 1) S-b-18 SA S-b-174MeOPh H 5-Bzt C 420 (M⁺ + 1) S-b-19 SB Int.s-5 BRA10 4MeOPh Me 3-Qu C428 (M⁺ + 1) S-b-20 SA S-b-19 4MeOPh H 3-Qu C 414 (M⁺ + 1) S-b-21 SBInt.s-5 BRA11 4MeOPh Me 6-Qu C 428 (M⁺ + 1) S-b-22 SA S-b-21 4MeOPH H6-Qu C 414 (M⁺ + 1) S-b-23 SB Int.s-5 BRA12 4MeOPh Me 6-IQ C 428(M⁺ + 1) S-b-24 SA S-b-23 4MeOPH H 6-IQ C 414 (M⁺ + 1) S-b-25 SB Int.s-7BRA1 2MeOPh Me 2-Nap C 427 (M⁺ + 1) S-b-26 SA S-b-25 2MeOPh H 2-Nap C413 (M⁺ + 1) S-b-27 SB Int.s-7 BRA2 2MeOPh Me 5-Ind C 416 (M⁺ + 1)S-b-28 SA S-b-27 2MeOPh H 5-Ind C 402 (M⁺ + 1) S-b-29 SB Int.s-7 BRA52MeOPh Me 5-1HIdz C 417 (M⁺ + 1) S-b-30 SA S-b-29 2MeOPh H 5-1HIdz C 403(M⁺ + 1) S-b-31 SB Int.s-7 BRA10 2MeOPh Me 3-Qu C 428 (M⁺ + 1) S-b-32 SAS-b-31 2MeOPh H 3-Qu C 414 (M⁺ + 1) S-b-33 SB Int.s-9 BRA1 3MeOPh Me2-Nap C 427 (M⁺ + 1) S-b-34 SA S-b-33 3MeOPh H 2-Nap C 413 (M⁺ + 1)S-b-35 SB Int.s-9 BRA3 3MeOPh Me 1Me-5-Ind C 430 (M⁺ + 1) S-b-36 SAS-b-35 3MeOPh H 1Me-5-Ind C 416 (M⁺ + 1) S-b-37 SB Int.s-9 BRA6 3MeOPhMe 1Me-5-1HIdz C 431 (M⁺ + 1) S-b-38 SA S-b-37 3MeOPh H 1Me-5-1HIdz C417 (M⁺ + 1) S-b-39 SB Int.s-9 BRA11 3MeOPh Me 6-Qu C 428 (M⁺ + 1)S-b-40 SA S-b-39 3MeOPh H 6-Qu C 414 (M⁺ + 1) S-b-41 SB Int.s-11 BRA22MePh Me 5-Ind C 400 (M⁺ + 1) S-b-42 SA S-b-41 2MePh H 5-Ind C 386(M⁺ + 1) S-b-43 SB Int.s-11 BRA3 2MePh Me 1Me-5-Ind C 414 (M⁺ + 1)S-b-44 SA S-b-43 2MePh H 1Me-5-Ind C 400 (M⁺ + 1) S-b-45 SB Int.s-11BRA5 2MePh Me 5-1HIdz C 401 (M⁺ + 1) S-b-46 SA S-b-45 2MePh H 5-1HIdz C387 (M⁺ + 1)

TABLE S-B-2 LCMS Exp. Syn SM1 SM2 Rx Y AR method RTime Mass S-b-47 SBInt.s-13 BRA3 3MePh Me 1Me-5-Ind C 414 (M⁺ + 1) S-b-48 SA N-b-47 3MePh H1Me-5-Ind C 400 (M⁺ + 1) S-b-49 SB Int.s-13 BRA6 3MePh Me 1Me-5-1HIdz C415 (M⁺ + 1) S-b-50 SA N-b-49 3MePh H 1Me-5-1HIdz C 401 (M⁺ + 1) S-b-51SB Int.s-13 BRA9 3MePh Me 5-Bzt C 418 (M⁺ + 1) S-b-52 SA N-b-51 3MePh H5-Bzt C 404 (M⁺ + 1) S-b-53 SB Int.s-15 BRA1 4MePh Me 2-Nap C 411(M⁺ + 1) S-b-54 SA N-b-53 4MePh H 2-Nap C 397 (M⁺ + 1) S-b-55 SBInt.s-15 BRA2 4MePh Me 5-Ind C 400 (M⁺ + 1) S-b-56 SA N-b-55 4MePh H5-Ind C 386 (M⁺ + 1) S-b-57 SB Int.s-15 BRA3 4MePh Me 1Me-5-Ind C 418(M⁺ + 1) S-b-58 SA N-b-57 4MePh H 1Me-5-Ind C 404 (M⁺ + 1) S-b-59 SBInt.s-17 BRA5 2FPh Me 5-1HIdz C 404 (M⁺ + 1) S-b-60 SA N-b-59 2FPh H5-1HIdz C 390 (M⁺ + 1) S-b-61 SB Int.s-17 BRA6 2FPh Me 1Me-5-Ind C 418(M⁺ + 1) S-b-62 SA N-b-61 2FPh H 1Me-5-Ind C 404 (M⁺ + 1) S-b-63 SBInt.s-17 BRA11 2FPh Me 6-Qu C 415 (M⁺ + 1) S-b-64 SA N-b-63 2FPh H 6-QuC 401 (M⁺ + 1) S-b-65 SB Int.s-19 BRA1 3FPh Me 2-Nap C 415 (M⁺ + 1)S-b-66 SA N-b-65 3FPh H 2-Nap C 401 (M⁺ + 1) S-b-67 SB Int.s-19 BRA23FPh Me 5-Ind C 403 (M⁺ + 1) S-b-68 SA N-b-67 3FPh H 5-Ind C 389(M⁺ + 1) S-b-69 SB Int.s-19 BRA6 3FPh Me 1Me-5-1HIdz C 418 (M⁺ + 1)S-b-70 SA N-b-69 3FPh H 1Me-5-1HIdz C 404 (M⁺ + 1) S-b-71 SB Int.s-21BRA3 4FPh Me 1Me-5-Ind C 418 (M⁺ + 1) S-b-72 SA N-b-71 4FPh H 1Me-5-IndC 404 (M⁺ + 1) S-b-73 SB Int.s-21 BRA5 4FPh Me 5-1HIdz C 404 (M⁺ + 1)S-b-74 SA N-b-73 4FPh H 5-1HIdz C 390 (M⁺ + 1) S-b-75 SB Int.s-21 BRA104FPh Me 3-Qu C 415 (M⁺ + 1) S-b-76 SA N-b-75 4FPh H 3-Qu C 401 (M⁺ + 1)S-b-77 SB Int.s-24 BRA1 cPen Me 2-Nap C 389 (M⁺ + 1) S-b-78 SA N-b-77cPen H 2-Nap C 375 (M⁺ + 1) S-b-79 SB Int.s-24 BRA2 cPen Me 5-Ind C 378(M⁺ + 1) S-b-80 SA N-b-79 cPen H 5-Ind C 364 (M⁺ + 1) S-b-81 SB Int.s-24BRA6 cPen Me 1Me-5-1HIdz C 407 (M⁺ + 1) S-b-82 SA N-b-81 cPen H1Me-5-1HIdz C 393 (M⁺ + 1) S-b-83 SB Int.s-27 BRA3 cHex Et 1Me-5-Ind C406 (M⁺ + 1) S-b-84 SA N-b-83 cHex H 1Me-5-Ind C 392 (M⁺ + 1) S-b-85 SBInt.s-27 BRA5 cHex Et 5-1HIdz C 393 (M⁺ + 1) S-b-86 SA N-b-85 cHex H5-1HIdz C 379 (M⁺ + 1) S-b-87 SB Int.s-27 BRA12 cHex Et 6-Qu C 363(M⁺ + 1) S-b-88 SA N-b-87 cHex H 6-Qu C 349 (M⁺ + 1) S-b-89 SB Int.s-30BRA1 nPr Et 2-Nap C 362 (M⁺ + 1) S-b-90 SA N-b-89 nPr H 2-Nap C 348(M⁺ + 1) S-b-91 SB Int.s-30 BRA2 nPr Et 5-Ind C 351 (M⁺ + 1) S-b-92 SAN-b-91 nPr H 5-Ind C 337 (M⁺ + 1)

TABLE S-B-3 LCMS Exp. Syn SM1 SM2 Rx Y AR method RTime Mass S-b-93 SBInt.s-30 BRA6 nPr Et 1Me-5-1HIdz C 366 (M⁺ + 1) S-b-94 SA N-b-93 nPr H1Me-5-1HIdz C 352 (M⁺ + 1) S-b-95 SB Int.s-33 BRA1 iPr Et 2-Nap C 362(M⁺ + 1) S-b-96 SA N-b-95 iPr H 2-Nap C 348 (M⁺ + 1) S-b-97 SB Int.s-33BRA3 iPr Et 1Me-5-Ind C 365 (M⁺ + 1) S-b-98 SA N-b-97 iPr H 1Me-5-Ind C351 (M⁺ + 1) S-b-99 SB Int.s-33 BRA5 iPr Et 5-1HIdz C 352 (M⁺ + 1)S-b-100 SA N-b-99 iPr H 5-1HIdz C 338 (M⁺ + 1) S-b-101 SB Int.s-36 BRA2nBu Et 5-Ind C 366 (M⁺ + 1) S-b-102 SA N-b-101 nBu H 5-Ind C 352(M⁺ + 1) S-b-103 SB Int.s-36 BRA5 nBu Et 5-1HIdz C 366 (M⁺ + 1) S-b-104SA N-b-103 nBu H 5-1HIdz C 352 (M⁺ + 1) S-b-105 SB Int.s-36 BRA11 nBu Et6-Qu C 378 (M⁺ + 1) S-b-106 SA N-b-105 nBu H 6-Qu C 364 (M⁺ + 1) S-b-107SB Int.s-39 BRA1 iBu Me 2-Nap C 377 (M⁺ + 1) S-b-108 SA N-b-107 iBu H2-Nap C 363 (M⁺ + 1) S-b-109 SB Int.s-39 BRA3 iBu Me 1Me-5-Ind C 380(M⁺ + 1) S-b-110 SA N-b-109 iBu H 1Me-5-Ind C 366 (M⁺ + 1) S-b-111 SBInt.s-39 BRA5 iBu Me 5-1HIdz C 366 (M⁺ + 1) S-b-112 SA N-b-111 iBu H5-1HIdz C 352 (M⁺ + 1) S-b-113 SB Int.s-39 BRA6 iBu Me 1Me-5-1HIdz C 381(M⁺ + 1) S-b-114 SA N-b-113 iBu H 1Me-5-1HIdz C 367 (M⁺ + 1) S-b-115 SBInt.s-42 BRA1 PhEt Me 2-Nap C 425 (M⁺ + 1) S-b-116 SA N-b-115 PhEt H2-Nap C 411 (M⁺ + 1) S-b-117 SB Int.s-42 BRA2 PhEt Me 5-Ind C 414(M⁺ + 1) S-b-118 SA N-b-117 PhEt H 5-Ind C 400 (M⁺ + 1) S-b-119 SBInt.s-42 BRA3 PhEt Me 1Me-5-Ind C 428 (M⁺ + 1) S-b-120 SA N-b-119 PhEt H1Me-5-Ind C 414 (M⁺ + 1) S-b-121 SB Int.s-45 BRA1 4MeOBn Et 2-Nap C 441(M⁺ + 1) S-b-122 SA N-b-121 4MeOBn H 2-Nap C 427 (M⁺ + 1) S-b-123 SBInt.s-45 BRA5 4MeOBn Et 5-1HIdz C 431 (M⁺ + 1) S-b-124 SA N-b-123 4MeOBnH 5-1HIdz C 417 (M⁺ + 1) S-b-125 SB Int.s-45 BRA6 4MeOBn Et 1Me-5-1HIdzC 431 (M⁺ + 1) S-b-126 SA N-b-125 4MeOBn H 1Me-5-1HIdz C 417 (M⁺ + 1)S-b-127 SB Int.s-48 BRA1 4FBn Et 2-Nap C 429 (M⁺ + 1) S-b-128 SA N-b-1274FBn H 2-Nap C 415 (M⁺ + 1) S-b-129 SB Int.s-48 BRA2 4FBn Et 5-Ind C 418(M⁺ + 1) S-b-130 SA N-b-129 4FBn H 5-Ind C 404 (M⁺ + 1) S-b-131 SBInt.s-48 BRA6 4FBn Et 1Me-5-1HIdz C 418 (M⁺ + 1) S-b-132 SA N-b-131 4FBnH 1Me-5-1HIdz C 404 (M⁺ + 1) S-b-133 SB Int.s-51 BRA3 2MeBn Et 1Me-5-IndC 428 (M⁺ + 1) S-b-134 SA N-b-133 2MeBn H 1Me-5-Ind C 414 (M⁺ + 1)S-b-135 SB Int.s-51 BRA5 2MeBn Et 5-1HIdz C 415 (M⁺ + 1) S-b-136 SAN-b-135 2MeBn H 5-1HIdz C 401 (M⁺ + 1) S-b-137 SB Int.s-51 BRA10 2MeBnEt 3-Qu C 426 (M⁺ + 1) S-b-138 SA N-b-137 2MeBn H 3-Qu C 412 (M⁺ + 1)

TABLE S-C-1

LCMS Exp. Syn SM1 SM2 Rx Y AR method RTime Mass S-c-1 SB Int.s-6 BRA14MeOPh Me 2-Nap C 429 (M⁺ + 1) S-c-2 SA S-c-1 4MeOPh H 2-Nap C 415(M⁺ + 1) S-c-3 SB Int.s-6 BRA2 4MeOPh Me 5-Ind C 418 (M⁺ + 1) S-c-4 SAS-c-3 4MeOPh H 5-Ind C 404 (M⁺ + 1) S-c-5 SB Int.s-6 BRA3 4MeOPh Me1Me-5-Ind C 432 (M⁺ + 1) S-c-6 SA S-c-5 4MeOPh H 1Me-5-Ind C 418(M⁺ + 1) S-c-7 SB Int.s-6 BRA4 4MeOPh Me 1Et-5-Ind C 446 (M⁺ + 1) S-c-8SA S-c-7 4MeOPh H 1Et-5-Ind C 432 (M⁺ + 1) S-c-9 SB Int.s-6 BRA5 4MeOPhMe 5-1HIdz C 419 (M⁺ + 1) S-c-10 SA S-c-9 4MeOPh H 5-1HIdz C 405(M⁺ + 1) S-c-11 SB Int.s-6 BRA6 4MeOPh Me 1Me-5-1HIdz C 433 (M⁺ + 1)S-c-12 SA S-c-11 4MeOPh H 1Me-5-1HIdz C 419 (M⁺ + 1) S-c-13 SB Int.s-6BRA7 4MeOPh Me 1Et-5-1HIdz C 447 (M⁺ + 1) S-c-14 SA S-c-13 4MeOPh H1Et-5-1HIdz C 433 (M⁺ + 1) S-c-15 SB Int.s-6 BRA8 4MeOPh Me 2Me-5-2HIdzC 433 (M⁺ + 1) S-c-16 SA S-c-15 4MeOPh H 2Me-5-2HIdz C 419 (M⁺ + 1)S-c-17 SB Int.s-6 BRA9 4MeOPh Me 5-Bzt C 436 (M⁺ + 1) S-c-18 SA S-c-174MeOPh H 5-Bzt C 422 (M⁺ + 1) S-c-19 SB Int.s-6 BRA10 4MeOPh Me 3-Qu C430 (M⁺ + 1) S-c-20 SA S-c-19 4MeOPh H 3-Qu C 416 (M⁺ + 1) S-c-21 SBInt.s-6 BRA11 4MeOPh Me 6-Qu C 430 (M⁺ + 1) S-c-22 SA S-c-21 4MeOPH H6-Qu C 416 (M⁺ + 1) S-c-23 SB Int.s-6 BRA12 4MeOPh Me 6-IQ C 430(M⁺ + 1) S-c-24 SA S-c-23 4MeOPH H 6-IQ C 416 (M⁺ + 1) S-c-25 SB Int.s-8BRA1 2MeOPh Me 2-Nap C 429 (M⁺ + 1) S-c-26 SA S-c-25 2MeOPh H 2-Nap C415 (M⁺ + 1) S-c-27 SB Int.s-8 BRA3 2MeOPh Me 1-Me-5-Ind C 431 (M⁺ + 1)S-c-28 SA S-c-27 2MeOPh H 1-Me-5-Ind C 418 (M⁺ + 1) S-c-29 SB Int.s-8BRA5 2MeOPh Me 5-1HIdz C 419 (M⁺ + 1) S-c-30 SA S-c-29 2MeOPh H 5-1HIdzC 405 (M⁺ + 1) S-c-31 SB Int.s-8 BRA10 2MeOPh Me 3-Qu C 430 (M⁺ + 1)S-c-32 SA S-c-31 2MeOPh H 3-Qu C 416 (M⁺ + 1) S-c-33 SB Int.s-10 BRA13MeOPh Me 2-Nap C 429 (M⁺ + 1) S-c-34 SA S-c-33 3MeOPh H 2-Nap C 415(M⁺ + 1) S-c-35 SB Int.s-10 BRA2 3MeOPh Me 5-Ind C 418 (M⁺ + 1) S-c-36SA .S-c-35 3MeOPh H 5-Ind C 403 (M⁺ + 1) S-c-37 SB Int.s-10 BRA6 3MeOPhMe 1Me-5-1HIdz C 433 (M⁺ + 1) S-c-38 SA S-c-37 3MeOPh H 1Me-5-1HIdz C419 (M⁺ + 1) S-c-39 SB Int.s-10 BRA11 3MeOPh Me 6-Qu C 430 (M⁺ + 1)S-c-40 SA S-c-39 3MeOPh H 6-Qu C 416 (M⁺ + 1) S-c-41 SB Int.s-12 BRA32MePh Me 1-Me-5-Ind C 402 (M⁺ + 1) S-c-42 SA S-c-41 2MePh H 1-Me-5-Ind C388 (M⁺ + 1) S-c-43 SB Int.s-12 BRA5 2MePh Me 5-1HIdz C 416 (M⁺ + 1)S-c-44 SA S-c-43 2MePh H 5-1HIdz C 402 (M⁺ + 1) S-c-45 SB Int.s-12 BRA62MePh Me 1Me-5-1HIdz C 417 (M⁺ + 1) S-c-46 SA S-c-45 2MePh H 1Me-5-1HIdzC 403 (M⁺ + 1)

TABLE S-C-2 LCMS Exp. Syn SM1 SM2 Rx Y AR method RTime Mass S-c-47 SBInt.s-14 BRA3 3MePh Me 1-Me-5-Ind C 416 (M⁺ + 1) S-c-48 SA N-c-47 3MePhH 1-Me-5-Ind C 402 (M⁺ + 1) S-c-49 SB Int.s-14 BRA6 3MePh Me1-Me-5-1HIdz C 417 (M⁺ + 1) S-c-50 SA N-c-49 3MePh H 1-Me-5-1HIdz C 403(M⁺ + 1) S-c-51 SB Int.s-14 BRA9 3MePh Me 5-Bzt C 420 (M⁺ + 1) S-c-52 SAN-c-51 3MePh H 5-Bzt C 406 (M⁺ + 1) S-c-53 SB Int.s-16 BRA1 4MePh Me2-Nap C 413 (M⁺ + 1) S-c-54 SA N-c-53 4MePh H 2-Nap C 399 (M⁺ + 1)S-c-55 SB Int.s-16 BRA2 4MePh Me 5-Ind C 402 (M⁺ + 1) S-c-56 SA N-c-554MePh H 5-Ind C 388 (M⁺ + 1) S-c-57 SB Int.s-16 BRA3 4MePh Me 1Me-5-IndC 420 (M⁺ + 1) S-c-58 SA N-c-57 4MePh H 1Me-5-Ind C 406 (M⁺ + 1) S-c-59SB Int.s-18 BRA5 2FPh Me 5-1HIdz C 406 (M⁺ + 1) S-c-60 SA N-c-59 2FPh H5-1HIdz C 392 (M⁺ + 1) S-c-61 SB Int.s-18 BRA6 2FPh Me 1Me-5-1HInd C 420(M⁺ + 1) S-c-62 SA N-c-61 2FPh H 1Me-5-1HInd C 406 (M⁺ + 1) S-c-63 SBInt.s-18 BRA11 2FPh Me 6-Qu C 418 (M⁺ + 1) S-c-64 SA N-c-63 2FPh H 6-QuC 404 (M⁺ + 1) S-c-65 SB Int.s-20 BRA1 3FPh Me 2-Nap C 417 (M⁺ + 1)S-c-66 SA N-c-65 3FPh H 2-Nap C 403 (M⁺ + 1) S-c-67 SB Int.s-20 BRA23FPh Me 5-Ind C 405 (M⁺ + 1) S-c-68 SA N-c-67 3FPh H 5-Ind C 391(M⁺ + 1) S-c-69 SB Int.s-20 BRA6 3FPh Me 1Me-5-1HIdz C 421 (M⁺ + 1)S-c-70 SA N-c-69 3FPh H 1Me-5-1HIdz C 407 (M⁺ + 1) S-c-71 SB Int.s-22BRA3 4FPh Me 1Me-5-Ind C 420 (M⁺ + 1) S-c-72 SA N-c-71 4FPh H 1Me-5-IndC 406 (M⁺ + 1) S-c-73 SB Int.s-22 BRA5 4FPh Me 5-1HIdz C 406 (M⁺ + 1)S-c-74 SA N-c-73 4FPh H 5-1HIdz C 392 (M⁺ + 1) S-c-75 SB Int.s-22 BRA104FPh Me 3-Qu C 418 (M⁺ + 1) S-c-76 SA N-c-75 4FPh H 3-Qu C 404 (M⁺ + 1)S-c-77 SB Int.s-25 BRA1 cPen Et 2-Nap C 391 (M⁺ + 1) S-c-78 SA N-c-77cPen H 2-Nap C 377 (M⁺ + 1) S-c-79 SB Int.s-25 BRA2 cPen Et 5-Ind C 380(M⁺ + 1) S-c-80 SA N-c-79 cPen H 5-Ind C 366 (M⁺ + 1) S-c-81 SB Int.s-25BRA6 cPen Et 1Me-5-1HIdz C 409 (M⁺ + 1) S-c-82 SA N-c-81 cPen H1Me-5-1HIdz C 395 (M⁺ + 1) S-c-83 SB Int.s-28 BRA3 cHex Et 1Me-5-Ind C408 (M⁺ + 1) S-c-84 SA N-c-83 cHex H 1Me-5-Ind C 394 (M⁺ + 1) S-c-85 SBInt.s-28 BRA5 cHex Et 5-1HIdz C 395 (M⁺ + 1) S-c-86 SA N-c-85 cHex H5-1HIdz C 381 (M⁺ + 1) S-c-87 SB Int.s-28 BRA12 cHex Et 6-Qu C 365(M⁺ + 1) S-c-88 SA N-c-87 cHex H 6-Qu C 351 (M⁺ + 1) S-c-89 SB Int.s-31BRA 1 nPr Et 2-Nap C 365 (M⁺ + 1) S-c-90 SA N-c-89 nPr H 2-Nap C 351(M⁺ + 1) S-c-91 SB Int.s-31 BRA2 nPr Et 5-Ind C 353 (M⁺ + 1) S-c-92 SAN-c-91 nPr H 5-Ind C 339 (M⁺ + 1)

TABLE S-C-3 LCMS Exp. Syn SM1 SM2 Rx Y AR method RTime Mass S-c-93 SBInt.s-31 BRA6 nPr Et 1Me-5-1HIdz C 368 (M⁺ + 1) S-c-94 SA N-c-93 nPr H1Me-5-1HIdz C 354 (M⁺ + 1) S-c-95 SB Int.s-34 BRA3 iPr Et 1Me-5-Ind C368 (M⁺ + 1) S-c-96 SA N-c-95 iPr H 1Me-5-Ind C 354 (M⁺ + 1) S-c-97 SBInt.s-34 BRA5 iPr Et 5-1HIdz C 354 (M⁺ + 1) S-c-98 SA N-c-97 iPr H5-1HIdz C 340 (M⁺ + 1) S-c-99 SB Int.s-34 BRA12 iPr Et 6-IQ C 380(M⁺ + 1) S-c-100 SA N-c-99 iPr H 6-IQ C 366 (M⁺ + 1) S-c-101 SB Int.s-37BRA1 nBu Et 2-Nap C 379 (M⁺ + 1) S-c-102 SA N-c-101 nBu H 2-Nap C 365(M⁺ + 1) S-c-103 SB Int.s-37 BRA2 nBu Et 5-Ind C 368 (M⁺ + 1) S-c-104 SAN-c-103 nBu H 5-Ind C 354 (M⁺ + 1) S-c-105 SB Int.s-37 BRA6 nBu Et1Me-5-1HIdz C 383 (M⁺ + 1) S-c-106 SA N-c-105 nBu H 1Me-5-1HIdz C 369(M⁺ + 1) S-c-107 SB Int.s-40 BRA1 iBu Et 2-Nap C 379 (M⁺ + 1) S-c-108 SAN-c-107 iBu H 2-Nap C 365 (M⁺ + 1) S-c-109 SB Int.s-40 BRA3 iBu Et1Me-5-Ind C 382 (M⁺ + 1) S-c-110 SA N-c-109 iBu H 1Me-5-Ind C 368(M⁺ + 1) S-c-111 SB Int.s-40 BRA5 iBu Et 5-1HIdz C 369 (M⁺ + 1) S-c-112SA N-c-111 iBu H 5-1HIdz C 355 (M⁺ + 1) S-c-113 SB Int.s-40 BRA6 iBu Et1Me-5-1HIdz C 383 (M⁺ + 1) S-c-114 SA N-c-113 iBu H 1Me-5-1HIdz C 369(M⁺ + 1) S-c-115 SB Int.s-43 BRA1 PhEt Et 2-Nap C 427 (M⁺ + 1) S-c-116SA N-c-115 PhEt H 2-Nap C 413 (M⁺ + 1) S-c-117 SB Int.s-43 BRA2 PhEt Et5-Ind C 416 (M⁺ + 1) S-c-118 SA N-c-117 PhEt H 5-Ind C 402 (M⁺ + 1)S-c-119 SB Int.s-43 BRA6 PhEt Et 1Me-5-1HIdz C 431 (M⁺ + 1) S-c-120 SAN-c-119 PhEt H 1Me-5-1HIdz C 417 (M⁺ + 1) S-c-121 SB Int.s-46 BRA14MeOBn Et 2-Nap C 443 (M⁺ + 1) S-c-122 SA N-c-121 4MeOBn H 2-Nap C 429(M⁺ + 1) S-c-123 SB Int.s-46 BRA3 4MeOBn Et 1Me-5-Ind C 446 (M⁺ + 1)S-c-124 SA N-c-123 4MeOBn H 1Me-5-Ind C 432 (M⁺ + 1) S-c-125 SB Int.s-46BRA5 4MeOBn Et 5-1HIdz C 419 (M⁺ + 1) S-c-126 SA N-c-125 4MeOBn H5-1HIdz C 405 (M⁺ + 1) S-c-127 SB Int.s-49 BRA1 4FBn Et 2-Nap C 431(M⁺ + 1) S-c-128 SA N-c-127 4FBn H 2-Nap C 417 (M⁺ + 1) S-c-129 SBInt.s-49 BRA2 4FBn Et 5-Ind C 420 (M⁺ + 1) S-c-130 SA N-c-129 4FBn H5-Ind C 406 (M⁺ + 1) S-c-131 SB Int.s-49 BRA5 4FBn Et 5-1HIdz C 406(M⁺ + 1) S-c-132 SA N-c-131 4FBn H 5-1HIdz C 392 (M⁺ + 1) S-c-133 SBInt.s-52 BRA3 2MeBn Et 1Me-5-Ind C 430 (M⁺ + 1) S-c-134 SA N-c-133 2MeBnH 1Me-5-Ind C 416 (M⁺ + 1) S-c-135 SB Int.s-52 BRA6 2MeBn Et 1Me-5-1HIdzC 431 (M⁺ + 1) S-c-136 SA N-c-135 2MeBn H 1Me-5-1HIdz C 417 (M⁺ + 1)S-c-137 SB Int.s-52 BRA11 2MeBn Et 6-Qu C 428 (M⁺ + 1) S-c-138 SAN-c-137 2MeBn H 6-Qu C 414 (M⁺ + 1)

Example S-d-1 Synthesis of ethyl3-{4-[(4-methoxyphenyl)methylsulfinyl]-3-(naphthalen-2-yl)phenyl}propionate(Compound No. S-d-1) (Synthesis method SG)

A solution of the compound of Example S-c-121 (130.9 mg) indichloromethane (4 ml) was added with 3-chloroperoxybenzoic acid (60.0mg, TCI), and stirred at room temperature for 1.5 hours. The reactionmixture was added with water (10 ml), extracted with dichloromethane (20ml), and then washed with saturated brine. The organic layer was dried,and then the solvent was evaporated under reduced pressure. The residuewas purified by column chromatography (Quad, chloroform:methanol=30:1)to obtain the title compound (Compound No. S-d-1, 108.7 mg).

Example S-d-7 Synthesis of ethyl3-{4-[(4-methoxyphenyl)methylsulfonyl]-3-(naphthalen-2-yl)phenyl}propionate(Compound No. S-d-7) (Synthesis method SG)

A solution of the compound of Example S-c-121 (53.1 mg) indichloromethane (3 ml) was added with 3-chloroperoxybenzoic acid (74.5mg, TCI), and stirred at room temperature for 5 hours. The reactionmixture was added with water (10 ml), extracted with dichloromethane (20ml), and then washed with saturated brine. The organic layer was dried,and then the solvent was evaporated under reduced pressure. The residuewas purified by column chromatography (Quad, hexane:ethyl acetate=4:1)to obtain the title compound (Compound No. S-d-7, 48.1 mg).

Examples S-d-1 to S-d-36

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-S-D-1. In the tables, thecompound numbers are mentioned in the columns indicated as “Exp.”. Inthe tables, used methods among the aforementioned synthesis methods areshown in the columns of “Syn” with symbols, and the starting compounds 1are mentioned in the columns of “SM1”.

TABLE S-D-1

LCMS Exp. Syn SM1 RS(O)n Y AR method RTime Mass S-d-1 SG S-c-1214MeOBnSO Et 2-Nap C 473 (M⁺ + 1) S-d-2 SA S-d-1 4MeOBnSO H 2-Nap C 445(M⁺ + 1) S-d-3 SG S-c-123 4MeOBnSO Et 1-Me-5-Ind C 476 (M⁺ + 1) S-d-4 SAS-d-3 4MeOBnSO H 1-Me-5-Ind C 448 (M⁺ + 1) S-d-5 SG S-c-125 4MeOBnSO Et5-1HIdz C 463 (M⁺ + 1) S-d-6 SA S-d-5 4MeOBnSO H 5-1HIdz C 435 (M⁺ + 1)S-d-7 SG S-c-121 4MeOBnSO2 Et 2-Nap C 489 (M⁺ + 1) S-d-8 SA S-d-74MeOBnSO2 H 2-Nap C 461 (M⁺ + 1) S-d-9 SG S-c-123 4MeOBnSO2 Et1-Me-5-Ind C 492 (M⁺ + 1) S-d-10 SA S-d-9 4MeOBnSO2 H 1-Me-5-Ind C 464(M⁺ + 1) S-d-11 SG S-c-125 4MeOBnSO2 Et 5-1HIdz C 479 (M⁺ + 1) S-d-12 SAS-d-11 4MeOBnSO2 H 5-1HIdz C 451 (M⁺ + 1) S-d-13 SG S-c-77 cPenSO Et2-Nap C 421 (M⁺ + 1) S-d-14 SA S-d-13 cPenSO H 2-Nap C 393 (M⁺ + 1)S-d-15 SG S-c-79 cPenSO Et 5-Ind C 410 (M⁺ + 1) S-d-16 SA S-d-15 cPenSOH 5-Ind C 381 (M⁺ + 1) S-d-17 SG S-c-81 cPenSO Et 1Me-5-1HIdz C 425(M⁺ + 1) S-d-18 SA S-d-17 cPenSO H 1Me-5-1HIdz C 397 (M⁺ + 1) S-d-19 SGS-c-77 cPenSO2 Et 2-Nap C 437 (M⁺ + 1) S-d-20 SA S-d-19 cPenSO2 H 2-NapC 409 (M⁺ + 1) S-d-21 SG S-c-79 cPenSO2 Et 5-Ind C 426 (M⁺ + 1) S-d-22SA S-d-21 cPenSO2 H 5-Ind C 397 (M⁺ + 1) S-d-23 SG S-c-81 cPenSO2 Et1Me-5-1HIdz C 441 (M⁺ + 1) S-d-24 SA S-d-23 cPenSO2 H 1Me-5-1HIdz C 413(M⁺ + 1) S-d-25 SG S-c-101 nBuSO Et 2-Nap C 409 (M⁺ + 1) S-d-26 SAS-d-25 nBuSO H 2-Nap C 377 (M⁺ + 1) S-d-27 SG S-c-103 nBuSO Et 5-Ind C398 (M⁺ + 1) S-d-28 SA S-d-27 nBuSO H 5-Ind C 365 (M⁺ + 1) S-d-29 SGS-c-105 nBuSO Et 1Me-5-1HIdz C 413 (M⁺ + 1) S-d-30 SA S-d-29 nBuSO H1Me-5-1HIdz C 381 (M⁺ + 1) S-d-31 SG S-c-101 nBuSO2 Et 2-Nap C 425(M⁺ + 1) S-d-32 SA S-d-31 nBuSO2 H 2-Nap C 397 (M⁺ + 1) S-d-33 SGS-c-103 nBuSO2 Et 5-Ind C 410 (M⁺ + 1) S-d-34 SA S-d-33 nBuSO2 H 5-Ind C385 (M⁺ + 1) S-d-35 SG S-c-105 nBuSO2 Et 1Me-5-1HIdz C 425 (M⁺ + 1)S-d-36 SA S-d-35 nBuSO2 H 1Me-5-1HIdz C 401 (M⁺ + 1)

Reference Examples Intermediates An-1 to An-5 Synthesis of ethyl3-[2-hydroxy-3-(naphthalen-2-yl)pyridin-5-yl]propionate (IntermediateAh-1)

A solution of the compound of Example P-42 (452 mg) in a mixture ofethyl acetate (5 ml) and methanol (2.5 ml) was added with 10%palladium/carbon (50 mg), and stirred at room temperature for 2 hoursunder hydrogen atmosphere. The reaction mixture was filtered, and thesolvent of the filtrate was evaporated under reduced pressure to obtainthe title compound (Intermediate Ah-1,321 mg). Mass (FAB): 322 (M⁺+1).

Synthesis of ethyl3-[3-(naphthalen-2-yl)-2-(trifluoromethanesulfonyl)pyridin-5-yl]propionate(Intermediate An-1)

According to the procedure described in the synthesis method ofIntermediate Aa-1, Intermediate Ah-1 (310 mg) andtrifluoromethanesulfonic anhydride (170 μl) were reacted and treated toobtain the title compound (Intermediate An-1, 355 mg). Mass (FAB): 454(M⁺+1).

Typical examples of the reaction intermediates that can be obtained byreacting and treating corresponding starting compounds according to themethod described above are shown below.

-   Intermediate An-2: ethyl    3-[3-(1H-indol-5-yl)-2-(trifluoromethanesulfonyl)pyridin-5-yl]propionate-   Intermediate An-3: ethyl    3-[3-(1-methyl-1H-indol-5-yl)-2-(trifluoromethanesulfonyl)pyridin-5-yl]propionate-   Intermediate An-4: ethyl    3-[3-(1H-indazol-5-yl)-2-(trifluoromethanesulfonyl)pyridin-5-yl]propionate-   Intermediate An-5: ethyl    3-[3-(1-methyl-1H-indazol-5-yl)-2-(trifluoromethanesulfonyl)pyridin-5-yl]propionate

Examples Cn-1 to Cn-45

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compoundsaccording to the methods described in Examples Ca-1 and Ca-2 are shownin Table-Cn-1.

In the table, the substances mentioned in the column of “SM1” correspondto reaction intermediates, and the substances mentioned in the column of“SM2” correspond to the boronic acid reagent used in Example Ca-1. Theboronic acid reagents indicated with the symbols of “BRA (number)” inthe columns of “SM2” are those mentioned in Table-Ba-1 and Table-Ba-2.

TABLE Cn-1

LCMS Exp. Rx Y AR SM1 SM2 method RTime Mass Cn-1 Ph Et 2-Nap An-1 BRA-14D 382 (M⁺ + 1) Cn-2 Ph H 2-Nap Cn-1 — C 354 (M⁺ + 1) Cn-3 Ph Et 5-IndAn-2 BRA14 C 371 (M⁺ + 1) Cn-4 Ph H 5-Ind Cn-3 — C 343 (M⁺ + 1) Cn-5 PhEt 1-Me-5-Ind An-3 BRA14 C 385 (M⁺ + 1) Cn-6 Ph H 1-Me-5-Ind Cn-5 — C357 (M⁺ + 1) Cn-7 Ph Et 5-1HIdz An-4 BRA14 C 372 (M⁺ + 1) Cn-8 Ph H5-1HIdz Cn-7 — C 344 (M⁺ + 1) Cn-9 Ph Et 1Me-5-1HIdz An-5 BRA14 C 386(M⁺ + 1) Cn-10 Ph H 1Me-5-1HIdz Cn-9 — C 358 (M⁺ + 1) Cn-11 4MeOPh H2-Nap An-1 BRA19 C 384 (M⁺ + 1) Cn-12 4MeOPh H 5-Ind An-2 BRA19 C 373(M⁺ + 1) Cn-13 4MeOPh H 5-1HIdz An-4 BRA19 C 374 (M⁺ + 1) Cn-14 4MeOPh H1Me-5-1HIdz An-5 BRA19 C 388 (M⁺ + 1) Cn-15 3MeOPh H 2-Nap An-1 BRA37 C384 (M⁺ + 1) Cn-16 2MeOPh H 2-Nap An-1 BRA38 C 384 (M⁺ + 1) Cn-17 2MeOPhH 1-Me-5-Ind An-3 BRA38 C 387 (M⁺ + 1) Cn-18 2MeOPh H 1-Me-5-1HIdz An-5BRA38 C 388 (M⁺ + 1) Cn-19 2MePh H 2-Nap An-1 BRA59 C 368 (M⁺ + 1) Cn-202MePh H 1Me-5-Ind An-3 BRA59 C 371 (M⁺ + 1) Cn-21 2MePh H 1Me-5-1HIdzAn-5 BRA59 C 372 (M⁺ + 1) Cn-22 3MePh H 2-Nap An-1 BRA60 C 368 (M⁺ + 1)Cn-23 3MePh H 5-1HIdz An-4 BRA60 C 358 (M⁺ + 1) Cn-24 4MePh H 2-Nap An-1BRA29 C 368 (M⁺ + 1) Cn-25 4MePh H 5-Ind An-2 BRA29 C 357 (M⁺ + 1) Cn-264MePh H 1-Me-5-Ind An-3 BRA29 C 371 (M⁺ + 1) Cn-27 4MePh H 5-1HIdz An-4BRA29 C 358 (M⁺ + 1) Cn-28 4MePh H 1Me-5-1HIdz An-5 BRA29 C 372 (M⁺ + 1)Cn-29 4CF₃Ph H 5-Ind An-2 BRA41 C 411 (M⁺ + 1) Cn-30 4CF₃Ph H 5-1HIdzAn-4 BRA41 C 412 (M⁺ + 1) Cn-31 4CF₃Ph H 1Me-5-1HIdz An-5 BRA41 C 426(M⁺ + 1) Cn-32 4ClPh H 5-Ind An-2 BRA30 C 377 (M⁺ + 1) Cn-33 4ClPh H1Me-5-Ind An-3 BRA30 C 391 (M⁺ + 1) Cn-34 4ClPh H 1Me-5-1HIdz An-5 BRA30C 392 (M⁺ + 1) Cn-35 2FPh H 2-Nap An-1 BRA32 C 372 (M⁺ + 1) Cn-36 2FPh H1Me-5-Ind An-3 BRA32 C 375 (M⁺ + 1) Cn-37 2FPh H 5-1HIdz An-4 BRA32 C362 (M⁺ + 1) Cn-38 2FPh H 1Me-5-1HIdz An-5 BRA32 C 376 (M⁺ + 1) Cn-393FPh H 5-Ind An-2 BRA33 C 361 (M⁺ + 1) Cn-40 3FPh H 5-1HIdz An-4 BRA33 C362 (M⁺ + 1) Cn-41 3FPh H 1Me-5-1HIdz An-5 BRA33 C 376 (M⁺ + 1) Cn-424FPh H 2-Nap An-1 BRA34 C 372 (M⁺ + 1) Cn-43 4FPh H 5-Ind An-2 BRA34 C361 (M⁺ + 1) Cn-44 4FPh H 5-1HIdz An-4 BRA34 C 362 (M⁺ + 1) Cn-45 4FPh H1Me-5-1HIdz An-5 BRA34 C 376 (M⁺ + 1)

Reference Examples Intermediates Int. n-1 to Int. n-115 Synthesis ofmethyl 3-(4-aminophenyl)propionate (Intermediate Int. n-1) (Synthesismethod NL)

A solution obtained beforehand by adding thionyl chloride (6.7 ml, WAKO)dropwise to methanol (50 ml) under ice cooling and mixing them was addeddropwise with a solution of 4-aminohydrocinnamic acid (9.97 g, TCI) inmethanol (50 ml) under ice cooling, stirred for 30 minutes, then warmedto room temperature, and further stirred for 16.5 hours. The reactionmixture was concentrated under reduced pressure, and then extracted withethyl acetate (200 ml), and the organic layer was washed successivelywith saturated aqueous sodium hydrogencarbonate, saturated aqueousammonium chloride and saturated brine. The organic layer was dried, andthen the solvent was evaporated under reduced pressure to obtain thetitle compound (Intermediate Int. n-1, 13.13 g).

Synthesis of methyl 3-(4-amino-3-bromophenyl)propionate (IntermediateInt. n-2) (Synthesis method NK)

A solution of Intermediate Int. n-1 (9.93 g) in acetic acid (55 ml) wasadded with potassium bromide (6.60 g, WAKO) and sodium tungstenate(IV)dihydrate (18.23 g, WAKO), stirred for 5 minutes, then added dropwisewith aqueous hydrogen peroxide (3.5 ml, WAKO) at 0° C. over 5 minutes,warmed to room temperature, and then stirred for 1 hour. The reactionmixture was poured into 5% aqueous ammonia containing ice, therebyadjusted to pH of about 6, and then added with dichloromethane (200 ml)for extraction. The organic layer was washed successively with saturatedaqueous ammonium chloride, saturated aqueous sodium hydrogencarbonateand saturated brine, and then dried, and the solvent was evaporatedunder reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=3:1) to obtain the titlecompound (Intermediate Int. n-2, 3.07 g).

Synthesis of methyl 3-(4-benzylamino-3-bromophenyl)propionate(Intermediate Int. n-3) (Synthesis method NC1)

A solution of Intermediate Int. n-2 (10.97 g) in methanol (30 ml) wasadded with benzaldehyde (5.25 ml, TCI) and anhydrous sodium sulfate(6.49 g, WAKO), and stirred at 60° C. for 13 hours. The reaction mixturewas added with sodium cyanotrihydroridoborate (2.73 g, WAKO), andfurther stirred for 5 hours. The reaction mixture was concentrated underreduced pressure, and then extracted with dichloromethane (150 ml), andthe organic layer was washed with saturated brine, and dried. Then, thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=4:1) to obtain thetitle compound (Intermediate Int. n-3, 13.45 g).

Synthesis of methyl 3-[3-bromo-(4-fluorobenzylamino)phenyl]propionate(Intermediate Int. n-4) (Synthesis method NC2)

A solution of Intermediate Int. n-2 (5.80 g) in dichloromethane (100 ml)was added with p-fluorobenzaldehyde (2.83 ml, TCI), sodiumtriacetoxyborohydride (7.14 g, Ald) and acetic acid (1.4 ml), andstirred at room temperature for 19 hours. The reaction mixture wasextracted with dichloromethane (300 ml), and the organic layer waswashed with saturated brine, and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=4:1) to obtain the titlecompound (Intermediate Int. n-4, 7.51 g).

Synthesis of methyl 3-[4-amino-3-(naphthalen-2-yl)phenyl]propionate(Intermediate Int. n-7) (Synthesis method ND1)

A solution of the compound of Example N-a-1 (3.01 g) in a mixture ofmethanol (40 ml) and THF (20 ml) was added with 10% palladium/carbon(410.3 mg, Merck) and one drop of concentrated hydrochloric acid, andstirred at room temperature for 5 hours under hydrogen atmosphere. Thereaction mixture was filtered, and the solvent of the filtrate wasevaporated under reduced pressure. The residue was added with ethylacetate (200 ml), and washed successively with saturated aqueous sodiumhydrogencarbonate and saturated brine, and then dried, and the solventwas evaporated under reduced pressure to obtain the title compound(Intermediate Int. n-7, 2.58 g).

Synthesis of methyl 3-[3-nitro-4-(piperazin-1-yl)phenyl]acrylate(Intermediate Int. n-19) (Synthesis method NJ)

A solution of methoxycarbonylmethyl(triphenyl)phosphonium bromide (1.1g, TCI) in THF (12.5 ml) was added with sodium hydride (115 mg, WAKO)under ice cooling, warmed to room temperature, then added dropwise witha solution of 3-nitro-4-(piperazin-1-yl)benzaldehyde (550.6 mg, MAYB) inTHF (12.5 ml), and stirred at the same temperature for 16.5 hours. Thereaction mixture was poured into brine (40 ml), and extracted with ethylacetate (100 ml). The organic layer was washed successively withsaturated aqueous sodium hydrogencarbonate and saturated brine, anddried, and then the solvent was evaporated under reduced pressure. Theresidue was purified by flash column chromatography (hexane:ethylacetate=5:1) to obtain the title compound (Intermediate Int. n-19, 511mg).

Synthesis of methyl 3-[3-amino-4-(piperazin-1-yl)phenyl]propionate(Intermediate Int. n-20) (Synthesis method ND1)

According to the procedure described in the synthesis method ofIntermediate Int. n-7 (Synthesis method ND1) provided that the reactionwas carried out in ethyl acetate for 13 hours, Intermediate Int. n-19(505 mg) and 10% palladium/carbon (50 mg) were reacted and treated toobtain the title compound (Intermediate Int. n-20, 658.9 mg).

Synthesis of methyl 3-[3-bromo-4-(piperazin-1-yl)phenyl]propionate(Intermediate Int. n-21) (Synthesis method NI)

A solution of hydrobromic acid (570 μl) in methanol (2.3 ml) was addeddropwise with a solution of Intermediate Int. n-20 (235 mg) in methanol(2.3 ml) over 10 minutes under ice cooling. This reaction mixture wasadded with an aqueous solution (250 μl) of sodium nitrite (69 mg, WAKO).The reaction mixture was added dropwise with an aqueous solution (2.3ml) of copper(II) bromide (222 mg, WAKO) heated to 50° C. over 15minutes, stirred for 4 hours at the same temperature, and then furtherstirred at room temperature for 12.5 hours. The reaction mixture waspoured into aqueous sodium hydrogencarbonate (20 ml), and extracted withethyl acetate (40 ml). The organic layer was washed with saturatedbrine, and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by flash column chromatography(hexane:ethyl acetate=4:1) to obtain the title compound (IntermediateInt. n-21, 89 mg).

Synthesis of methyl 4-fluoro-3-bromocinnamate (Intermediate Int. n-25)(Synthesis method NL)

According to the procedure described in the synthesis method ofIntermediate Int. n-1 (Synthesis method NL) provided that the reactionwas carried out for 1 hour, 3-bromo-4-fluorocinnamic acid (3.30 g, LANC)and thionyl chloride (1.5 ml) were reacted and treated to obtain thetitle compound (Intermediate Int. n-25, 3.47 g)

Synthesis of methyl 3-[3-bromo-4-(piperidin-1-yl)phenyl]cinnamate(Intermediate Int. n-26) (Synthesis method NG)

A solution of Intermediate Int. n-25 (136.4 mg) in DMSO (5 ml) was addedwith potassium carbonate (109.8 mg) and piperidine (84.8 μl, TCI), andstirred at 90° C. for 15 hours. The reaction mixture was extracted withethyl acetate (50 ml), and then the organic layer was washedsuccessively with saturated aqueous sodium hydrogencarbonate, saturatedaqueous ammonium chloride and saturated brine, and dried. Then, thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:isopropyl ether=6:1) to obtainthe title compound (Intermediate Int. n-26, 120.4 mg).

Synthesis of methyl 3-[3-bromo-4-(piperidin-1-yl)phenyl]propionate(Intermediate Int. n-27) (Synthesis method ND2)

According to a procedure described in literature [D. J. Hart et al.,Journal of Organic Chemistry (J. Org. Chem.), 1987, vol. 52, p. 4665], asolution of Intermediate Int. n-26 (690.6 mg) in dimethoxyethane (100ml) was added with p-toluenesulfonhydrazide (2.97 g, TCI), and refluxedby heating at 110° C. Then, the reaction mixture was added dropwise withan aqueous solution (100 ml) of sodium acetate (2.85 g, WAKO) over 2hours, and further stirred for 1 hour. The reaction mixture wasextracted with dichloromethane (450 ml), and the organic layer waswashed with water, and dried, and then the solvent was evaporated underreduced pressure. The residue was purified by column chromatography(Quad, hexane:ethyl acetate=6:1) to obtain the title compound(Intermediate Int. n-27, 648.2 mg).

Synthesis of 3-bromo-(4-imidazol-1-yl)benzaldehyde (Intermediate Int.n-32) (Synthesis method NG)

According to the procedure described in the synthesis method ofIntermediate Int. n-26 (Synthesis method NG) provided that the reactionwas performed for 20 hours, and the column chromatography was performedwith chloroform:methanol=100:1, 3-bromo-4-fluorobenzaldehyde (1.246 g,TCI), potassium carbonate (825.1 mg) and imidazole (444 mg, TCI) werereacted and treated to obtain the title compound (Intermediate Int.n-32, 986.1 mg).

Synthesis of ethyl 3-[3-bromo-(4-imidazol-1-yl)phenyl]acrylate(Intermediate Int. n-33) (Synthesis method NJ)

A solution of Intermediate Int. n-32 (986.1 mg) and ethyldiethylphosphonoacetate (705 μl) in 1,2-dimethoxyethane (8 ml) was addedwith 60% sodium hydride (180.2 mg) under ice cooling, stirred for 10minutes, then warmed to room temperature, and stirred for 1 hour. Thereaction mixture was added with dichloromethane (60 ml) for extraction,and the organic layer was washed with saturated brine, and dried. Then,the solvent was evaporated under reduced pressure. The residue waspurified by column chromatography (Quad, dichloromethane:methanol=100:1)to obtain the title compound (Intermediate Int. n-33, 1.00 g).

Synthesis of methyl 3-(4-cyclopentylaminophenyl)propionate (IntermediateInt. n-38) (Synthesis method NC1)

According to the procedure described in the synthesis method ofIntermediate Int. n-3 provided that the reaction was carried out for 6hours, Intermediate Int. n-1 (1.03 g), cyclopentanone (450 μl, TCI),sodium triacetoxyborohydride (1.56 g) and acetic acid (350 μl) werereacted and treated to obtain the title compound (Intermediate Int.n-37, 1.21 g).

Synthesis of methyl 3-(4-cyclopentylamino-3,5-dibromophenyl)propionate(Intermediate Int. n-39) (Synthesis method NK)

A solution of Intermediate Int. n-37 (1.21 g) in acetonitrile was warmedto 35° C., then added with N-bromosuccinimide (2.44 g, TCI), and stirredfor 1 hour. The reaction mixture was concentrated under reducedpressure, then added with ethyl acetate (150 ml), washed successivelywith aqueous sodium thiosulfate, saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride and saturatedbrine, and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:ethyl acetate=6:1) to obtain the title compound (IntermediateInt. n-38, 1.41 g).

Synthesis of 2-bromopyridine-5-carbaldehyde (Intermediate Int. n-44)(Synthesis method NM)

According to a procedure described in literature (Xin Wang et al.,Tetrahedron. Lett., 2000, vol. 41, p. 4335], a solution of2,5-dibromopyridine (3.17 g) in anhydrous diethyl ether (140 ml) wasadded dropwise with a 1.6 M solution of n-butyl lithium in hexane (11ml) with cooling at −78° C. under argon gas atmosphere over 5 minutes,and stirred for 20 minutes. This reaction mixture was added dropwisewith dehydrated DMF (1 ml) over 3 minutes, stirred for 30 minutes, thenwarmed to room temperature, and further stirred for 1 hour. The reactionmixture was added with water (20 ml), and extracted with ethyl acetate(30 ml×2). The organic layer was washed with saturated brine, and dried,and then the solvent was evaporated under reduced pressure. The residuewas purified by column chromatography (Quad, hexane:ethyl acetate=6:1)to obtain the title compound (Intermediate Int. n-44, 1.46 g).

Synthesis of ethyl 3-(2-bromopyridin-5-yl)acrylate (Intermediate Int.n-45) (Synthesis method NJ)

According to the procedure described in the synthesis method ofIntermediate n-7 provided that the reaction was carried out for 15minutes, Intermediate Int. n-44 (1.45 g), ethyl diethylphosphonoacetate(2.1 ml) and 60% sodium hydride (355 mg) were reacted and treated toobtain the title compound (Intermediate Int. n-45, 1.87 g).

Synthesis of ethyl 3-[2-(piperidin-1-yl)pyridin-5-yl]acrylate(Intermediate Int. n-46) (Synthesis method NG)

Intermediate Int. n-45 (565.7 mg) was added with potassium carbonate(286.4 mg) and piperidine (3 ml), and stirred at 90° C. for 21 hours.The reaction mixture was added with ethyl acetate (50 ml), washedsuccessively with saturated aqueous sodium hydrogencarbonate, saturatedaqueous ammonium chloride and saturated brine, and dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=4:1) to obtain thetitle compound (Intermediate Int. n-46, 165.9 mg).

Synthesis of ethyl 3-[2-(piperidin-1-yl)pyridin-5-yl]propionate(Intermediate Int. n-47) (Synthesis method ND1)

According to the procedure described in the synthesis method ofIntermediate Int. n-7 with the modifications that the reaction wascarried out for 1 hour, and the purification was performed by columnchromatography (Quad, hexane:ethyl acetate 6:1), Intermediate Int. n-46(392 mg) and 10% palladium/carbon (30 mg) were reacted and treated toobtain the title compound (Intermediate Int. n-47; 246 mg).

Synthesis of ethyl 3-[3-bromo-2-(piperidin-1-yl)pyridin-3-yl]propionate(Intermediate Int. n-48) (Synthesis method NK2)

A solution of Intermediate Int. n-47 (242 mg) in acetonitrile was addedwith bromine (84 μl), and stirred at 40° C. for 1 hour. The reactionmixture was concentrated under reduced pressure, then added with ethylacetate (50 ml), washed successively with aqueous sodium thiosulfate,saturated aqueous sodium hydrogencarbonate, saturated aqueous ammoniumchloride and saturated brine, and dried, and then the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=6:1) to obtain the titlecompound (Intermediate Int. n-48, 224 mg).

Synthesis of 2-benzylaminopyridine-5-carbaldehyde (Intermediate Int.n-59) (Synthesis Method NG)

Intermediate Int. n-44 (102.0 mg) was added with benzylamine (1 ml,TCI), and stirred at 120° C. for 39 hours. The reaction mixture wasadded with ethyl acetate (50 ml), washed successively with saturatedaqueous sodium hydrogencarbonate, saturated aqueous ammonium chlorideand saturated brine, and dried, and then the solvent was evaporatedunder reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=4:1) to obtain the titlecompound (Intermediate Int. n-59, 58.3 mg).

Synthesis of 2-benzylamino-3-bromopyridine-5-carbaldehyde (IntermediateInt. n-60) (Synthesis method NK)

A solution of Intermediate Int. n-59 (56.8 mg) in acetonitrile was addedwith N-bromosuccinimide (134 mg), and stirred at room temperature for 14hours. The reaction mixture was concentrated under reduced pressure,then added with ethyl acetate (50 ml), washed successively with aqueoussodium thiosulfate, saturated aqueous sodium hydrogencarbonate,saturated aqueous ammonium chloride and saturated brine, and dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by column chromatography (Quad, hexane:ethyl acetate=4:1) toobtain the title compound (Intermediate Int. n-60, 50 mg).

Synthesis of ethyl 3-(2-benzylamino-3-bromopyridin-5-yl)acrylate(Intermediate Int. n-61) (Synthesis method NJ)

According to the procedure described in the synthesis method ofIntermediate Int. n-7 provided that the reaction was carried out for 30minutes, Intermediate Int. n-60 (49.1 g), ethyl diethylphosphonoacetate(92 μl) and 60% sodium hydride (30 mg) were reacted and treated toobtain the title compound (Intermediate Int. n-61, 28 mg).

Synthesis of ethyl 3-(2-benzylamino-3-bromopyridin-5-yl)propionate(Intermediate Int. n-62) (Synthesis method ND2)

According to the procedure described in the synthesis method ofIntermediate Int. n-27 provided that the reaction was carried out for 4hours, Intermediate Int. n-60 (49.1 mg), p-toluenesulfonhydrazide (320.6mg) and sodium acetate (412.4 mg) were reacted and treated to obtain thetitle compound (Intermediate Int. n-62, 38.9 mg).

Synthesis of methyl 3-(4-amino-3-bromo-5-nitrophenyl)propionate(Intermediate Int. n-76) (Synthesis method NM)

A solution obtained by adding potassium nitrate (1.10 g) to a solutionof Intermediate Int. n-2 (2.57 g) in acetic anhydride (20 ml) under icecooling and stirring them for 10 minutes was added dropwise withconcentrated sulfuric acid (700 μl) over 10 minutes. The reactionmixture was stirred for 10 minutes at the same temperature, then warmedto room temperature, and further stirred for 30 minutes. The reactionmixture was poured into 1 N aqueous sodium hydroxide (250 ml) containingice, and extracted with isopropyl ether (200 ml×2). The organic layerwas washed successively with saturated aqueous sodium hydrogencarbonateand saturated brine, and dried, and then the solvent was evaporatedunder reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=3:1) to obtain the titlecompound (Intermediate Int. n-76, 0.72 g).

Typical examples of the intermediates for synthesizing the compounds ofthe present invention that can be obtained by reacting and treatingcorresponding starting compounds using any of the methods described inthe present specification are shown in Table-Int. N-1 to Table-Int. N-8.In the tables, the intermediate numbers “Int. n-(number)” are mentionedin the columns indicated as “Exp.”. In the tables, used methods amongthe aforementioned synthesis methods are shown in the columns of “Syn”with symbols, the starting compounds 1 are mentioned in the columns of“SM1”, and the starting compounds 2 are mentioned in the columns of“SM2”. Further, the compounds indicated as “Single” in the columns of“Single or Double” in the tables are compound in which two of the carbonatoms binding the benzene ring and carbonyl group in the compounds arebound with a single bond, and those indicated as “Double” in the sameare compounds in which two of the carbon atoms binding the benzene ringand carbonyl group in the compounds are bound with a double bond. Thealdehydes and ketones used for the synthesis of the compounds arementioned in Table-Carb, and amines used for the same are mentioned inTable-AMN.

TABLE Carb Reagent Aldehyde or Ketone Manufacture CHO1 HCHO WAKO CHO2CH₃CHO Aldlich CHO3 CH₃CH₂CHO TCI CHO4 nPrCHO TCI CHO5 Acetone WAKO CHO6nBuCHO TCI CHO7 iPrCHO TCI CHO8 BnCHO TCI CHO9 4FBnCHO TCI CHO10 2FBnCHOTCI CHO11 3FBnCHO TCI CHO12 2ClBnCHO TCI CHO13 2BrBnCHO TCI CHO142,3DFBnCHO TCI CHO15 3,4DFBnCHO TCI CHO16 4PhBnCHO TCI CHO17 2CF₃BnCHOTCI CHO18 2,3DClBnCHO TCI CHO19 2-ThiofeneCHO(2-TFCHO) TCI CHO203-ThiofeneCHO(3-TFCHO) TCI CHO21 2-FuranCHO(2-FRCHO) TCI CHO22Cyclopentanone TCI CHO23 Cyclohexanone TCI CHO24 2(Me)cHexanone TCICHO25 2-Indanone Aldlich

TABLE AMN Reagent Amine Manufacture AMN1

TCI AMN2

TCI AMN3

TCI AMN4

TCI AMN5

TCI AMN6

TCI AMN7

TCI AMN8 EtMeNH Aldrich AMN9 Et₂NH Aldrich AMN10 nPrMeNH Aldrich AMN11iPrMeNH Aldrich AMN12 nBuMeNH Aldrich AMN13 nBuEtNH Aldrich AMN14iBuMeNH Aldrich AMN15 4MeBnNH₂ Aldrich AMN16 3MeBnNH₂ Aldrich AMN172MeBnNH₂ Aldrich AMN18 4FBnNH₂ Aldrich AMN19 3FBnNH₂ Aldrich AMN202FBnNH₂ Aldrich AMN21 3MeOBnNH₂ Aldrich AMN22 4MeOBnNH₂ Aldrich AMN232MeOBnNH₂ Aldrich AMN24 4CF₃BnNH₂ Aldrich AMN25 2EtOBnNH₂ Aldrich AMN263iPrOBnNH₂ Sigma-Aldrich AMN27 3,5DFBnNH₂ Aldrich

TABLE Int.N-1

LCMS meth- Exp. Syn SM1 SM2 Rz od RTime Mass Int.n-5 NC2 Int.n-2 CHO102FBn C 366 (M⁺) Int.n-6 NC1 Int.n-2 CHO11 3FBn C 366 (M⁺) Int.n-12 NC2Int.n-2 CHO2 Et C 386 (M⁺) Int.n-13 NC2 Int.n-2 CHO3 nPr D 5.02 300 (M⁺)Int.n-14 NC2 Int.n-2 CHO5 iPr D 5.38 341 (M⁺) Int.n-15 NC2 Int.n-2 CHO7iBu D 5.50 400 (M⁺) Int.n-16 NC2 Int.n-2 CHO22 cPen C 326 (M⁺) Int.n-17NC2 Int.n-2 CHO23 cHex C 340 (M⁺) Int.n-18 NC2 Int.n-2 CHO24 2(Me)cHex C354 (M⁺)

TABLE Int.N-2

LCMS Exp. Syn SM1 AR method RTime Mass Int.s-8 ND1 N-a-3 5-Ind C 295(M⁺ + 1) Int.n-9 ND1 N-a-5 1Me-5-Ind C 309 (M⁺ + 1) Int.n-10 ND1 N-a-75-1Idz C 296 (M⁺ + 1) Int.n-11 ND1 N-a-9 1Me-5- C 310 (M⁺ + 1) 1HIdz

TABLE Int.N-3

Single or LCMS Exp. Syn. RS G Double method RTime Mass Int.n-22 NJ

NO2 Double A 3.91 293 (M⁺ + 1) Int.n-23 ND1

NH2 Single A 2.97 265 (M⁺ + 1) Int.n-24 NI

Br Single A 4.31 328 (M⁺)

TABLE Int.N-4

Single or LCMS Exp. Syn SM1 RzRyN Double method RTime Mass Int.n-28 NC2Int.n-25

Double A 6.54 338 (M⁺) Int.n-29 NC1 Int.n-28

Single A 6.01 342 (M⁺ + 1) Int.n-30 NC2 Int.n-25

Double A 6.29 340 (M⁺ + 1) Int.n-31 NC2 Int.n-30

Single A 6.12 342 (M⁺ + 1) Int.n-33 NC2 Int.n-32

Double C 307 (M⁺) Int.n-35 NC2 Int.n-32

Double C 306 (M⁺) Int.n-36 NC2 Int.n-25

Double A 5.60 310 (M⁺) Int.n-37 NC2 Int.n-32

Double C 326 (M⁺)

TABLE Int.N-5

LCMS Exp. Syn SM1 RzRyN method RTime Mass Int.n-32 NC2 Int.n-25

C 351 (M⁺) Int.n-34 NC2 Int.n-25

C 250 (M⁺)

TABLE-Int.N-6

LCMS H or Exp. Syn SM1 SM2 Rz Z′ Br method RTime Mass Int.n-40 NC1Int.n-1 CHO3 nPr H H C 222 (M⁺ + 1) Int.n-41 NK Int.n-40 nPr Br Br C 380(M⁺ + 1) Int.n-42 NC1 Int.n-1 CHO5 iPr H H C 222 (M⁺ + 1) Int.n-43 NKInt.n-42 iPr Br Br C 380 (M⁺ + 1)

TABLE-Int.N-7

LCMS Exp. Syn RzRyN method RTime Mass Int.n-48 NG cHex C 327 (M⁺)Int.n-49 NG cPen C 313 (M⁺) Int.n-50 NG 4(Me)cHex C 341 (M⁺) Int.n-51 NG

C 343 (M⁺) Int.n-52 NG cHep C 355 (M⁺) LCMS Exp. Syn Rz Ry method RTimeMass Int.n-53 NG Et Me C 301 (M⁺) Int.n-54 NG Et Et C 315 (M⁺) Int.n-55NG nPr Me C 315 (M⁺) Int.n-56 NG iPr Me C 315 (M⁺) Int.n-57 NG nBu Me C329 (M⁺) Int.n-58 NG iBu Me C 329 (M⁺) Int.n-63 NG 4MeBn H C 363 (M⁺)Int.n-64 NG 3MeBn H C 363 (M⁺) Int.n-65 NG 2MeBn H C 363 (M⁺) Int.n-66NG 4FBn H C 368 (M⁺+ 1) Int.n-67 NG 3FBn H C 368 (M⁺+ 1) Int.n-68 NG2FBn H C 368 (M⁺+ 1) Int.n-69 NG 4MeOPh H C 365 (M⁺) Int.n-70 NG 3MeOPhH C 365 (M⁺) Int.n-71 NG 2MeOPh H C 365 (M⁺) Int.n-72 NG 4CF3Ph H C 403(M⁺) Int.n-73 NG 2EtOPh H C 380 (M⁺+ 1) Int.n-74 NG 3iPrOPh H C 393 (M⁺)Int.n-75 NG 3,5DFPh H C 372 (M⁺+ 1)

TABLE-Int.N-8

LCMS Exp. Syn SM1 SM2 Rz Ry method RTime Mass Int.n-77 NC2 Int.n-76CHO22 cPen H C 371 (M⁺) Int.n-78 NC2 Int.n-76 CHO3 nPr H C 345 (M⁺)Int.n-79 NC2 Int.n-76 CHO5 iPr H C 345 (M⁺) Int.n-80 NC2 Int.n-76 CHO252-Indane H C 419 (M⁺) Int.n-81 NC2 Int.n-76 CHO23 cHex H C 385 (M⁺)Int.n-82 NC2 Int.n-76 CHO24 2(Me)cHex H C 399 (M⁺) Int.n-83 NC1 Int.n-77CHO1 cPen Me C 385 (M⁺) Int.n-84 NC1 Int.n-78 CHO1 nPr Me C 359 (M⁺)Int.n-85 NC1 Int.n-79 CHO1 iPr Me C 359 (M⁺) Int.n-86 NC1 Int.n-80 CHO12-Indane Me C 433 (M⁺) Int.n-87 NC1 Int.n-81 CHO1 cHex Me C 399 (M⁺)Int.n-88 NC1 Int.n-82 CHO1 2(Me)cHex Me C 413 (M⁺) Int.n-89 NC1 Int.n-76CHO8 Bn H C 393 (M⁺) Int.n-90 NC1 Int.n-76 CHO9 4FBn H C 411 (M⁺)Int.n-91 NC2 Int.n-76 CHO10 2FBn H C 411 (M⁺) Int.n-92 NC2 Int.n-76CHO11 3FBn H C 411 (M⁺) Int.n-93 NC2 Int.n-76 CHO14 2,3DFBn H C 429 (M⁺)Int.n-94 NC2 Int.n-76 CHO15 3,4DFBn H C 429 (M⁺) Int.n-95 NC2 Int.n-76CHO16 4PhBn H C 469 (M⁺) Int.n-96 NC2 Int.n-76 CHO17 2CF3Bn H C 461 (M⁺)Int.n-97 NC2 Int.n-76 CHO19 2-TF H C 399 (M⁺) Int.n-98 NC2 Int.n-76CHO20 3-TF H C 399 (M⁺) Int.n-99 NC2 Int.n-76 CHO21 2-FR H C 383 (M⁺)Int.n-100 NC1 Int.n-89 CHO1 Bn Me C 407 (M⁺) Int.n-101 NC1 Int.n-90 CHO14FBn Me C 428 (M⁺) Int.n-102 NC1 Int.n-91 CHO1 2FBn Me C 425 (M⁺)Int.n-103 NC1 Int.n-92 CHO1 3FBn Me C 425 (M⁺) Int.n-104 NC1 Int.n-93CHO1 2,3DFBn Me C 443 (M⁺) Int.n-105 NC1 Int.n-94 CHO1 3,4DFBn Me C 443(M⁺) Int.n-106 NC1 Int.n-95 CHO1 4PhBn Me C 483 (M⁺) Int.n-107 NC1Int.n-96 CHO1 2CF3Bn Me C 475 (M⁺) Int.n-108 NC1 Int.n-97 CHO1 2-TF Me C413 (M⁺) Int.n-109 NC1 Int.n-98 CHO1 3-TF Me C 413 (M⁺) Int.n-110 NC1Int.n-99 CHO1 2-FR Me C 397 (M⁺) LCMS Exp. Syn SM1 SM2 RzRyN methodRTime Mass Int.n-111 NM Int.n-21

C 357 (M⁺) Int.n-112 NM Int.n-24

C 373 (M⁺) Int.n-113 NM Int.n-27

C 371 (M⁺) Int.n-114 NM Int.n-29

C 385 (M⁺) Int.n-115 NM Int.n-31

C 385 (M⁺)

Example N-a-1 Synthesis of methyl3-[4-benzylamino-3-(naphthalen-2-yl)phenyl]propionate (Compound No.N-a-1) (Synthesis method NB1)

A solution of Intermediate n-3 (8.18 g) in toluene (60 ml) was addedwith 2-naphthaleneboronic acid (5.04 g, TCI), 2 M aqueous sodiumcarbonate (21.6 ml), methanol (24 ml) and tetrakistriphenylphosphinepalladium(0) (henceforth abbreviated as “(Ph₃P)₄Pd”, 1.94 g, NacalaiTesque), and stirred at 90° C. for 15 hours. The reaction mixture wasadded with ethyl acetate (300 ml), and washed successively withsaturated aqueous sodium hydrogencarbonate, saturated aqueous ammoniumchloride, and saturated brine. The organic layer was dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby flash column chromatography (hexane:ethyl acetate=3:1) to obtain thetitle compound (Compound No. N-a-1, 5.70 g).

Example N-a-2 Synthesis of3-[4-benzylamino-3-(naphthalen-2-yl)phenyl]propionic acid (Compound No.N-a-2) (Synthesis method NA)

A solution of the compound of Example N-a-1 (51 mg) in methanol (5.0 ml)was added with 2 N aqueous sodium hydroxide (130 μl), and stirred at 60°C. for 2 hours. The reaction mixture was concentrated under reducedpressure, then neutralized with 5% aqueous hydrochloric acid under icecooling, and then extracted with ethyl acetate (30 ml). The organiclayer was washed with saturated brine, and dried, and then the solventwas evaporated under reduced pressure to obtain the title compound(Compound No. N-a-2, 47 mg).

Example N-a-251 Synthesis of methyl3-[4-(N-benzyl-N-methylamino)-3-(naphthalen-2-yl)phenyl]propionate(Compound No. N-a-25) (Synthesis method NC1)

According to the procedure described in the synthesis method ofIntermediate n-3 provided that the reaction was carried out for 5 hours,the compound of Example N-a-1 (234.2 mg), 30% aqueous solution offormaldehyde (208.8 μl, WAKO) and sodium cyanotrihydroridoborate (140.9mg) were reacted and treated to obtain the title compound (Compound No.N-a-25, 176.3 mg).

Example N-A-137 Synthesis of methyl3-{3-(1-methyl-1H-indol-5-yl)-4-[N-(1-phenylethyl)amino]phenyl}propionate(Compound No. N-a-137) (Synthesis method NE1)

According to a procedure described in literature [Shin-Shyong Tseng etal., Journal of Organic Chemistry (J. Org. Chem.), 1979, vol. 44, p.4113], a solution of Intermediate n-9 (630.7 mg) in methylene chloride(10 ml) was added with triethylamine (405 μl, Kokusan Chemical), cooledto −78° C., then added dropwise with trifluoromethanesulfonyl chloride(426 μl, TCI), and stirred for 1.5 hours. The reaction mixture waspoured into ice water (10 ml), and added with dichloromethane (30 ml)for extraction. The organic layer was washed with saturated brine, anddried, and then the solvent was evaporated under reduced pressure toobtain a crude product. A solution of the obtained crude product in DMF(15 ml) was added with potassium carbonate (394.2 mg) and(1-bromoethyl)benzene (386.4 μl, TCI), and stirred at room temperaturefor 13 hours. The reaction mixture was extracted with ethyl acetate (100ml), and the organic layer was washed successively with saturatedaqueous sodium hydrogencarbonate, saturated aqueous ammonium chlorideand saturated brine, and dried. Then, the solvent was evaporated underreduced pressure. The residue was purified by column chromatography(Quad, hexane:ethyl acetate=4:1) to obtain the title compound (CompoundNo. N-a-137, 310.3 mg).

Example N-a-141 Synthesis of methyl3-[3-(1-methyl-1H-indol-5-yl)-4-{N-[2-(4-fluorophenyl)ethyl]amino}phenyl]propionate(Compound No. N-a-141) (Synthesis method NE2)

A solution of Intermediate n-9 (210.1 mg) in methylene chloride (10 ml)was added with triethylamine (135 μl, Kokusan Chemical), cooled to −78°C., then added dropwise with trifluoromethanesulfonyl chloride (143 μl,TCI), and stirred for 1.5 hours. The reaction mixture was poured intoice water (10 ml), and added with dichloromethane (15 ml) forextraction. The organic layer was washed with saturated brine, anddried, and then the solvent was evaporated under reduced pressure toobtain a crude product. A solution of the obtained crude product inanhydrous DMF (15 ml) was added with triphenylphosphine (485.9 g, WAKO),di-t-butyl azodicarboxylate (299.8 mg, Ald) and 4-fluorophenylethylalcohol (357 μl, TCI), and stirred at room temperature for 12 hours. Thereaction mixture was added with water (10 ml) and ethyl acetate (10 ml)for extraction, and the organic layer was washed successively withsaturated aqueous sodium hydrogencarbonate, saturated aqueous ammoniumchloride, and saturated brine, and dried. Then, the solvent wasevaporated under reduced pressure. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=4:1) to obtain the titlecompound (Compound No. N-a-141, 63.5 mg).

Example N-a-143 Synthesis of methyl3-[4-(N-acetyl-N-benzylamino)-3-(1-methyl-1H-indol-5-yl)phenyl]propionate(Compound No. N-a-143) (Synthesis method NF)

A solution of Compound No. N-a-5 (32 mg) in methylene chloride (3 ml)was added with pyridine (49.6 μl, TCI) and acetyl chloride (50 μl, TCI),and stirred for 13 hours. The reaction mixture was added with water (1ml), and the solvent was evaporated. The residue was purified by columnchromatography (Quad, hexane:ethyl acetate=4:1) to obtain the titlecompound (Compound No. N-a-143, 20.3 mg).

Example N-a-153 Synthesis of methyl3-[4-benzoylamino-3-(1-methyl-1H-indol-5-yl)phenyl]propionate (CompoundNo. N-a-153) (Synthesis method NF)

According to the procedure described in the synthesis method of thecompound of Example N-a-143 provided that the reaction was carried outfor 16 hours, Intermediate Int. n-9 (26.5 mg), pyridine (23.8 μl) andbenzoyl chloride (30 μl, WAKO) were reacted and treated to obtain thetitle compound (Compound No. N-a-153, 18.4 mg).

Examples N-a-1 to N-a-166

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-N-A-1 to Table-N-A-4. In thetables, the compound numbers are mentioned in the columns indicated as“Exp.”. In the tables, used methods among the aforementioned synthesismethods are shown in the columns of “Syn” with symbols, the startingcompounds 1 are mentioned in the columns of “SM1”, and the startingcompounds 2 are mentioned in the columns of “SM2”.

TABLE-N-A-1

LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-a-1 NB1 Int.n-3BRN1 Bn H Me H 2-Nap C 396 (M⁺ + 1) N-a-2 NA N-a-1 Bn H H H 2-Nap C 382(M⁺ + 1) N-a-3 NB1 Int.n-3 BRN2 Bn H Me H 5-1Ind C 385 (M⁺ + 1) N-a-4 NAN-a-3 Bn H H H 5-1Ind C 371 (M⁺ + 1) N-a-5 NB1 Int.n-3 BRN3 Bn H Me H1Me-5-Ind C 399 (M⁺ + 1) N-a-6 NA N-a-5 Bn H H H 1Me-5-Ind C 385(M⁺ + 1) N-a-7 NB1 Int.n-3 BRN4 Bn H Me H 1Et-5-Ind C 413 (M⁺ + 1) N-a-8NA N-a-7 Bn H H H 1Et-5-Ind C 399 (M⁺ + 1) N-a-9 NB1 Int.n-3 BRN5 Bn HMe H 5-1HIdz C 386 (M⁺ + 1) N-a-10 NA N-a-9 Bn H H H 5-1HIdz C 372(M⁺ + 1) N-a-11 NB1 Int.n-3 BRN6 Bn H Me H 1Me-5-1HIdz C 400 (M⁺ + 1)N-a-12 NA N-a-11 Bn H H H 1Me-5-1HIdz C 386 (M⁺ + 1) N-a-13 NB1 Int.n-3BRN7 Bn H Me H 1Et-5-1HIdz C 414 (M⁺ + 1) N-a-14 NA N-a-13 Bn H H H1Et-5-1HIdz C 400 (M⁺ + 1) N-a-15 NB1 Int.n-3 BRN8 Bn H Me H 2Me-5-2HIdzC 400 (M⁺ + 1) N-a-16 NA N-a-15 Bn H H H 2Me-5-2HIdz C 386 (M⁺ + 1)N-a-17 NB1 Int.n-3 BRN9 Bn H Me H 5-Bzt C 403 (M⁺ + 1) N-a-18 NA N-a-17Bn H H H 5-Bzt C 389 (M⁺ + 1) N-a-19 NB1 Int.n-3 BRN10 Bn H Me H 3-Qu C397 (M⁺ + 1) N-a-20 NA N-a-19 Bn H H H 3-Qu C 383 (M⁺ + 1) N-a-21 NB1Int.n-3 BRN11 Bn H Me H 6-Qu C 397 (M⁺ + 1) N-a-22 NA N-a-21 Bn H H H6-Qu C 383 (M⁺ + 1) N-a-23 NB1 Int.n-3 BRN12 Bn H Me H 6-IQ C 397(M⁺ + 1) N-a-24 NA N-a-23 Bn H H H 6-IQ C 383 (M⁺ + 1) N-a-25 NC1 N-a-1CHO1 Bn Me Me H 2-Nap C 410 (M⁺ + 1) N-a-26 NA N-a-25 Bn Me H H 2-Nap C396 (M⁺ + 1) N-a-27 NC1 N-a-1 CHO2 Bn Et Me H 2-Nap C 424 (M⁺ + 1)N-a-28 NA N-a-27 Bn Et H H 2-Nap C 410 (M⁺ + 1) N-a-29 NC1 N-a-3 CHO1 BnMe Me H 5-1Ind C 399 (M⁺ + 1) N-a-30 NA N-a-29 Bn Me H H 5-1Ind C 384(M⁺ + 1) N-a-31 NC1 N-a-5 CHO1 Bn Me Me H 1Me-5-Ind C 413 (M⁺ + 1)N-a-32 NA N-a-31 Bn Me H H 1Me-5-Ind C 399 (M⁺ + 1) N-a-33 NB1 Int.n-4BRA1 4FBn H Me H 2-Nap C 414 (M⁺ + 1) N-a-34 NA N-a-33 4FBn H H H 2-NapC 400 (M⁺ + 1) N-a-35 NB1 Int.n-4 BRA2 4FBn H Me H 5-1Ind D 5.20 403(M⁺ + 1) N-a-36 NA N-a-35 4FBn H H H 5-1Ind D 4.73 389 (M⁺ + 1) N-a-37NB1 Int.n-4 BRA3 4FBn H Me H 1Me-5-Ind D 5.51 417 (M⁺ + 1) N-a-38 NAN-a-37 4FBn H H H 1Me-5-Ind D 4.78 403 (M⁺ + 1) N-a-39 NB1 Int.n-4 BRA54FBn H Me H 5-1HIdz D 4.60 404 (M⁺ + 1) N-a-40 NA N-a-39 4FBn H H H5-1HIdz C 390 (M⁺ + 1) N-a-41 NB1 Int.n-4 BRA6 4FBn H Me H 1Me-5-1HIdz A4.85 418 (M⁺ + 1) N-a-42 NA N-a-41 4FBn H H H 1Me-5-1HIdz A 4.14 404(M⁺ + 1) N-a-43 NB1 Int.n-4 BRA10 4FBn H Me H 3-Qu D 4.72 415 (M⁺ + 1)N-a-44 NA N-a-43 4FBn H H H 3-Qu C 401 (M⁺ + 1)

TABLE N-A-2 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-a-45NC2 N-a-35 CHO1 4FBn Me Me H 5-Ind D 4.17 417 (M⁺ + 1) N-a-46 NA N-a-454FBn Me H H 5-Ind D 3.38 403 (M⁺ + 1) N-a-47 NC2 N-a-37 CHO1 4FBn Me MeH 1Me-5-Ind C 431 (M⁺ + 1) N-a-48 NA N-a-47 4FBn Me H H 1Me-5-Ind C 418(M⁺ + 1) N-a-49 NC2 N-a-41 CHO1 4FBn Me Me H 1Me-5-1HIdz C 432 (M⁺ + 1)N-a-50 NA N-a-49 4FBn Me H H 1Me-5-1HIdz C 418 (M⁺ + 1) N-a-51 NC2N-a-37 CHO2 4FBn Et Me H 1Me-5-Ind C 445 (M⁺ + 1) N-a-52 NA N-a-51 4FBnEt H H 1Me-5-Ind C 431 (M⁺ + 1) N-a-53 NC2 N-a-39 CHO2 4FBn Et Me H5-1Idz C 433 (M⁺ + 1) N-a-54 NA N-a-53 4FBn Et H H 5-1Idz C 419 (M⁺ + 1)N-a-55 NB1 Int.n-5 2FBn H Me H 2-Nap C 414 (M⁺ + 1) N-a-56 NA N-a-552FBn H H H 2-Nap C 400 (M⁺ + 1) N-a-57 NB1 Int.n-5 2FBn H Me H 1Me-5-IndC 417 (M⁺ + 1) N-a-58 NA N-a-57 2FBn H H H 1Me-5-Ind C 403 (M⁺ + 1)N-a-59 NB1 Int.n-5 2FBn H Me H 1Me-5-1HIdz C 418 (M⁺ + 1) N-a-60 NAN-a-59 2FBn H H H 1Me-5-1HIdz C 404 (M⁺ + 1) N-a-61 NC2 N-a-59 CHO1 2FBnMe Me H 1Me-5-1HIdz C 432 (M⁺ + 1) N-a-62 NA N-a-61 2FBn Me H H1Me-5-1HIdz C 418 (M⁺ + 1) N-a-63 NB1 Int.n-6 3FBn H Me H 2-Nap C 414(M⁺ + 1) N-a-64 NA N-a-63 3FBn H H H 2-Nap C 400 (M⁺ + 1) N-a-65 NB1Int.n-6 3FBn H Me H 5-1Ind C 403 (M⁺ + 1) N-a-66 NA N-a-65 3FBn H H H5-1Ind C 389 (M⁺ + 1) N-a-67 NB1 Int.n-6 3FBn H Me H 1Me-5-Ind C 417(M⁺ + 1) N-a-68 NA N-a-67 3FBn H H H 1Me-5-Ind C 403 (M⁺ + 1) N-a-69 NC2N-a-67 CHO1 3FBn Me Me H 1Me-5-Ind C 431 (M⁺ + 1) N-a-70 NA N-a-69 3FBnMe H H 1Me-5-Ind C 417 (M⁺ + 1) N-a-71 NC1 Int.n-7 CHO12 2ClBn H Me H2-Nap C 430 (M⁺ + 1) N-a-72 NA N-a-71 2ClBn H H H 2-Nap C 416 (M⁺ + 1)N-a-73 NC1 Int.n-7 CHO13 2BrBn H Me H 2-Nap C 475 (M⁺ + 1) N-a-74 NAN-a-73 2BrBn H H H 2-Nap C 461 (M⁺ + 1) N-a-75 NC1 Int.n-7 CHO14 2,3DFBnH Me H 2-Nap C 432 (M⁺ + 1) N-a-76 NA N-a-75 2,3DFBn H H H 2-Nap C 418(M⁺ + 1) N-a-77 NC1 Int.n-7 CHO21 2-FR H Me H 2-Nap C 386 (M⁺ + 1)N-a-78 NA N-a-77 2-FR H H H 2-Nap C 372 (M⁺ + 1) N-a-79 NC1 Int.n-7CHO20 3-TF H Me H 2-Nap C 402 (M⁺ + 1) N-a-80 NA N-a-79 3-TF H H H 2-NapC 388 (M⁺ + 1) N-a-81 NC1 Int.n-7 CHO17 2CF3Bn H Me H 2-Nap C 464(M⁺ + 1) N-a-82 NA N-a-80 2CF3Bn H H H 2-Nap C 450 (M⁺ + 1) N-a-83 NC1Int.n-8 CHO12 2ClBn H Me H 5-1Ind C 302 (M⁺ + 1) N-a-84 NA N-a-80 2ClBnH H H 5-1Ind C 288 (M⁺ + 1) N-a-85 NC2 N-a-80 CHO1 2ClBn Me Me H 5-1IndC 316 (M⁺ + 1) N-a-86 NA N-a-85 2ClBn Me H H 5-1Ind C 302 (M⁺ + 1)N-a-87 NC1 Int.n-8 CHO14 2,3DFBn H Me H 5-1Ind C 304 (M⁺ + 1) N-a-88 NAN-a-87 2,3DFBn H H H 5-1Ind C 290 (M⁺ + 1) N-a-89 NC1 Int.n-8 CHO164PhBn H Me H 5-1Ind C 344 (M⁺ + 1) N-a-90 NA N-a-89 4PhBn H H H 5-1Ind C330 (M⁺ + 1)

TABLE N-A-3 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-a-91NC1 Int.n-8 CHO19 2-TF H Me H 5-Ind C 391 (M⁺ + 1) N-a-92 NA N-a-91 2-TFH H H 5-Ind C 377 (M⁺ + 1) N-a-93 NC1 Int.n-8 CHO17 2CF3Bn H Me H 5-IndC 453 (M⁺ + 1) N-a-94 NA N-a-93 2CF3Bn H H H 5-Ind C 439 (M⁺ + 1) N-a-95NC1 Int.n-8 CHO18 2,3DClBn H Me H 5-Ind C 454 (M⁺ + 1) N-a-96 NA N-a-712,3DClBn H H H 5-Ind C 440 (M⁺ + 1) N-a-97 NC1 Int.n-9 CHO13 2BrBn H MeH 1Me-5-Ind C 478 (M⁺ + 1) N-a-98 NA N-a-97 2BrBn H H H 1Me-5-Ind C 464(M⁺ + 1) N-a-99 NC1 Int.n-9 CHO15 3,4DFBn H Me H 1Me-5-Ind C 435(M⁺ + 1) N-a-100 NA N-a-99 3,4DFBn H H H 1Me-5-Ind C 421 (M⁺ + 1)N-a-101 NC1 Int.n-9 CHO16 4PhBn H Me H 1Me-5-Ind C 475 (M⁺ + 1) N-a-102NA N-a-101 4PhBn H H H 1Me-5-Ind C 461 (M⁺ + 1) N-a-103 NC1 Int.n-9CHO21 2-FR H Me H 1Me-5-Ind C 389 (M⁺ + 1) N-a-104 NA N-a-103 2-FR H H H1Me-5-Ind C 375 (M⁺ + 1) N-a-105 NC1 Int.n-9 CHO20 3-TF H Me H 1Me-5-IndC 405 (M⁺ + 1) N-a-106 NA N-a-105 3-TF H H H 1Me-5-Ind C 391 (M⁺ + 1)N-a-107 NC1 Int.n-9 CHO18 2,3DClBn H Me H 1Me-5-Ind C 468 (M⁺ + 1)N-a-108 NA N-a-107 2,3DClBn H H H 1Me-5-Ind C 454 (M⁺ + 1) N-a-109 NC1Int.n-10 CHO13 2BrBn H Me H 5-1HIdz C 465 (M⁺ + 1) N-a-110 NA N-a-1092BrBn H H H 5-1HIdz C 451 (M⁺ + 1) N-a-111 NC1 Int.n-10 CHO15 3,4DFBn HMe H 5-1HIdz C 422 (M⁺ + 1) N-a-112 NA N-a-111 3,4DFBn H H H 5-1HIdz C408 (M⁺ + 1) N-a-113 NC2 N-a-111 CHO1 3,4DFBn Me Me H 5-1HIdz C 436(M⁺ + 1) N-a-114 NA N-a-113 3,4DFBn Me H H 5-1HIdz C 422 (M⁺ + 1)N-a-115 NC1 Int.n-10 CHO21 2-FR H Me H 5-1HIdz C 376 (M⁺ + 1) N-a-116 NAN-a-115 2-FR H H H 5-1HIdz C 362 (M⁺ + 1) N-a-117 NC1 Int.n-10 CHO203-TF H Me H 5-1HIdz C 392 (M⁺ + 1) N-a-118 NA N-a-116 3-TF H H H 5-1HIdzC 378 (M⁺ + 1) N-a-119 NC1 Int.n-10 CHO17 2CF3Bn H Me H 5-1HIdz C 454(M⁺ + 1) N-a-120 NA N-a-120 2CF3Bn H H H 5-1HIdz C 440 (M⁺ + 1) N-a-121NC1 Int.n-10 CHO18 2,3DClBn H Me H 1Me-5-1HIdz C 469 (M⁺ + 1) N-a-122 NAN-a-122 2,3DClBn H H H 1Me-5-1HIdz C 455 (M⁺ + 1) N-a-123 NC1 Int.n-11CHO12 2ClBn H Me H 1Me-5-1HIdz C 434 (M⁺ + 1) N-a-124 NA N-a-123 2ClBn HH H 1Me-5-1HIdz C 420 (M⁺ + 1) N-a-125 NC2 N-a-123 CHO1 2ClBn Me Me H1Me-5-1HIdz C 448 (M⁺ + 1) N-a-126 NA N-a-125 2ClBn Me H H 1Me-5-1HIdz C434 (M⁺ + 1) N-a-127 NC1 Int.n-11 CHO14 2,3DFBn H Me H 1Me-5-1HIdz C 436(M⁺ + 1) N-a-128 NA N-a-127 2,3DFBn H H H 1Me-5-1HIdz C 422 (M⁺ + 1)N-a-129 NC1 Int.n-11 CHO15 3,4DFBn H Me H 1Me-5-1HIdz C 436 (M⁺ + 1)N-a-130 NA N-a-129 3,4DFBn H H H 1Me-5-1HIdz C 422 (M⁺ + 1) N-a-131 NC1Int.n-11 CHO16 4PhBn H Me H 1Me-5-1HIdz C 476 (M⁺ + 1) N-a-132 NAN-a-131 4PhBn H H H 1Me-5-1HIdz C 462 (M⁺ + 1) N-a-133 NC1 Int.n-11CHO19 2-TF H Me H 1Me-5-1HIdz C 406 (M⁺ + 1) N-a-134 NA N-a-133 2-TF H HH 1Me-5-1HIdz C 392 (M⁺ + 1) N-a-135 NC1 Int.n-11 CHO17 2CF3Bn H Me H1Me-5-1HIdz C 468 (M⁺ + 1) N-a-136 NA N-a-135 2CF3Bn H H H 1Me-5-1HIdz C454 (M⁺ + 1)

TABLE-N-A-4 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-a-137 NE1 Int.n-9

H Me H 1Me-5-Ind C 413 (M⁺ + 1) N-a-138 NA N-a-137

H H H 1Me-5-Ind C 399 (M⁺ + 1) N-a-139 NE1 Int.n-11

H Me H 1Me-5-1HIdz D 5.06 414 (M⁺ + 1) N-a-140 NA N-a-139

H H H 1Me-5-1HIdz D 4.30 400 (M⁺ + 1) N-a-141 NE2 Int.n-11 2(4FPh)EtOH2(4FPh)Et H Me H 1Me-5-1HIdz D 5.08 432 (M⁺ + 1) N-a-142 NA N-a-1412(4FPh)Et H H H 1Me-5-1HIdz D 4.25 418 (M⁺ + 1) N-a-143 NF N-a-5 AcCl BnAc Me H 1Me-5-1HIdz C 444 (M⁺ + 1) N-a-144 NA N-a-143 Bn Ac H H1Me-5-1HIdz C 430 (M⁺ + 1) N-a-145 NF N-a-5 PhCOCl Bn PhC(O) Me H1Me-5-Ind C 504 (M⁺ + 1) N-a-146 NA N-a-145 Bn PhC(O) H H 1Me-5-Ind C490 (M⁺ + 1) N-a-147 NF N-a-5 MeOCH2COCl Bn MeOCH₂C(O) Me H 1Me-5-Ind C472 (M⁺ + 1) N-a-148 NA N-a-147 Bn MeOCH₂C(O) H H 1Me-5-Ind C 458(M⁺ + 1) N-a-149 NF N-a-5 MeOCOCl Bn MeOC(O) Me H 1Me-5-Ind C 458(M⁺ + 1) N-a-150 NA N-a-149 Bn MeOC(O) H H 1Me-5-Ind C 444 (M⁺ + 1)N-a-151 NF N-a-5 PhOCOCl Bn PhOC(O) Me H 1Me-5-Ind C 520 (M⁺ + 1)N-a-152 NA N-a-151 Bn PhOC(O) H H 1Me-5-Ind C 506 (M⁺ + 1) N-a-153 NFN-a-5 NMe2COCl Bn Me₂NC(O) Me H 1Me-5-Ind C 471 (M⁺ + 1) N-a-154 NAN-a-153 Bn Me₂NC(O) H H 1Me-5-Ind C 457 (M⁺ + 1) N-a-155 NF N-a-11 AcClBn Ac Me H 1Me-5-Ind C 442 (M⁺ + 1) N-a-156 NA N-a-155 Bn Ac H H1Me-5-Ind C 428 (M⁺ + 1) N-a-157 NF N-a-5 AcCl 4FBn Ac Me H 1Me-5-Ind C461 (M⁺ + 1) N-a-158 NA N-a-157 4FBn Ac H H 1Me-5-Ind C 447 (M⁺ + 1)N-a-159 NF N-a-5 MeOCH2COCl 4FBn MeOCH₂C(O) Me H 1Me-5-Ind C 491(M⁺ + 1) N-a-160 NA N-a-159 4FBn MeOCH₂C(O) H H 1Me-5-Ind C 477 (M⁺ + 1)N-a-161 NF N-a-5 MeOCOCl 4FBn MeOC(O) Me H 1Me-5-Ind C 477 (M⁺ + 1)N-a-162 NA N-a-161 4FBn MeOC(O) H H 1Me-5-Ind C 463 (M⁺ + 1) N-a-163 NFN-a-11 AcCl 4FBn Ac Me H 1Me-5-1HIdz C 462 (M⁺ + 1) N-a-164 NA N-a-1634FBn Ac H H 1Me-5-1HIdz C 448 (M⁺ + 1) N-a-165 NF N-a-11 MeOCOCl 4FBnMeOC(O) Me H 1Me-5-1HIdz C 478 (M⁺ + 1) N-a-166 NA N-a-165 4FBn MeOC(O)H H 1Me-5-1HIdz C 464 (M⁺ + 1)

Example N-b-1 Synthesis of methyl3-[4-(N-methylamino)-3-(naphthalen-2-yl)phenyl]propionate (Compound No.N-b-1) (Synthesis method ND1)

According to the procedure described in the synthesis method ofIntermediate Int. n-7 (Synthesis method ND1) provided that the reactionwas carried out for 2 hours, the compound of Example N-a-25 (100.3 mg)and 10% palladium/carbon (10.2 mg) were reacted and treated to obtainthe title compound (Compound No. N-b-1, 89.7 mg).

Example N-b-35 Synthesis of methyl3-[4-(N-ethylamino)-3-(naphthalen-2-yl)phenyl]propionate (Compound No.N-b-35) (Synthesis method NB1)

According to the procedure described in the synthesis method of thecompound of Example N-a-1 (Synthesis method NB1) provided that thereaction was carried out for 17 hours, Intermediate n-12 (99.87 mg),2-naphthaleneboronic acid (87.3 mg), 2 M aqueous sodium carbonate (350μl) and (Ph₃P)₄Pd (59.6 mg) were reacted and treated to obtain the titlecompound (Compound No. N-b-35, 103.5 mg).

Example N-b-79 Synthesis of methyl3-[4-(N-n-butylamino)-3-(naphthalen-2-yl)phenyl]propionate (Compound No.N-b-79) (Synthesis method NC2)

According to the procedure described in the synthesis method ofIntermediate n-3 provided that the reaction was carried out for 13hours, Intermediate n-7 (164.7 mg) and n-butylaldehyde (38.5 μl, KANTO),sodium triacetoxyborohydride (138.6 mg) and acetic acid (75 μl) werereacted and treated to obtain the title compound (Compound No. N-b-79,161.3 mg).

Example N-b-183 Synthesis of methyl3-[4-(N-acetyl-N-methylamino)-3-(naphthalen-2-yl)phenyl]propionate(Compound No. N-b-183) (Synthesis method NF)

According to the procedure described in the synthesis method of thecompound of Example N-a-143 provided that the reaction was carried outfor 18 hours, the compound of Example N-b-1 (22.7 mg), pyridine (23.8/1)and acetyl chloride (40 μl) were reacted and treated to obtain the titlecompound (Compound No. N-b-183, 16.3 mg).

Example N-b-197 Synthesis of3-[4-(N-benzoyl-N-methylamino)-3-(naphthalen-2-yl)phenyl]propionic acid(Compound No. N-b-197) (Synthesis method NF)

According to the procedure described in the synthesis method of thecompound of Example N-a-143 provided that the reaction was carried outfor 14 hours, the compound of Example N-b-1 (21.8 mg), pyridine (23.8μl) and benzoyl chloride (345 μl) were reacted and treated. A solutionof the obtained residue in methanol (3 ml) was added with 2 N aqueoussodium hydroxide (100 μl), and stirred at 60° C. for 2 hours. Thereaction mixture was concentrated under reduced pressure, then madeacidic with 5% aqueous hydrochloric acid under ice cooling, andextracted with dichloromethane (5 ml). The organic layer was washedsuccessively with saturated brine, and dried, and then the solvent wasevaporated under reduced pressure to obtain the title compound (CompoundNo. N-b-197, 13.5 mg).

Examples N-b-1 to N-b-212

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-N-B-1 to Table-N-B-5. In thetables, the compound numbers are mentioned in the columns indicated as“Exp.”. In the tables, used methods among the aforementioned synthesismethods are shown in the columns of “Syn” with symbols, the startingcompounds 1 are mentioned in the columns of “SM1”, and the startingcompounds 2 are mentioned in the columns of “SM2”.

TABLE-N-B-1

LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-b-1 ND1 N-a-25Me H Me H 2-Nap C 320 (M⁺ + 1) N-b-2 NA N-b-1 Me H H H 2-Nap C 306(M⁺ + 1) N-b-3 ND1 N-a-29 Me H Me H 5-Ind C 309 (M⁺ + 1) N-b-4 NA N-b-3Me H H H 5-Ind C 295 (M⁺ + 1) N-b-5 ND1 N-a-31 Me H Me H 1Me-5-Ind C 323(M⁺ + 1) N-b-6 NA N-b-5 Me H H H 1Me-5-Ind C 309 (M⁺ + 1) N-b-7 ND1N-a-69 Me H Me H 5-1HIdz C 310 (M⁺ + 1) N-b-8 NA N-b-7 Me H H H 5-1HIdzC 296 (M⁺ + 1) N-b-9 ND1 N-a-49 Me H Me H 1Me-5-1HIdz C 324 (M⁺ + 1)N-b-10 NA N-b-9 Me H H H 1Me-5-1HIdz C 310 (M⁺ + 1) N-b-11 NC2 N-b-1CHO1 Me Me Me H 2-Nap C 334 (M⁺ + 1) N-b-12 NA N-b-11 Me Me H H 2-Nap C320 (M⁺ + 1) N-b-13 NC2 N-b-1 CHO2 Me Et Me H 2-Nap C 348 (M⁺ + 1)N-b-14 NA N-b-13 Me Et H H 2-Nap C 334 (M⁺ + 1) N-b-15 NC2 N-b-3 CHO1 MeMe Me H 5-Ind C 323 (M⁺ + 1) N-b-16 NA N-b-15 Me Me H H 5-Ind C 309(M⁺ + 1) N-b-17 NC2 N-b-5 CHO1 Me Me H H 1Me-5-Ind C 337 (M⁺ + 1) N-b-18NA N-b-17 Me Me H H 1Me-5-Ind C 323 (M⁺ + 1) N-b-19 NC2 N-b-9 CHO1 Me MeMe H 1Me-5-1HIdz C 338 (M⁺ + 1) N-b-20 NA N-b-19 Me Me H H 1Me-5-1HIdz C324 (M⁺ + 1) N-b-21 NB1 Int.n-12 BRA1 Et H Me H 2-Nap C 334 (M⁺ + 1)N-b-22 NA N-b-21 Et H H H 2-Nap C 320 (M⁺ + 1) N-b-23 NB1 Int.n-12 BRA2Et H Me H 5-Ind C 323 (M⁺ + 1) N-b-24 NA N-b-23 Et H H H 5-Ind C 309(M⁺ + 1) N-b-25 NB1 Int.n-12 BRA3 Et H Me H 1Me-5-Ind C 337 (M⁺ + 1)N-b-26 NA N-b-25 Et H H H 1Me-5-Ind C 323 (M⁺ + 1) N-b-27 NB1 Int.n-12BRA4 Et H Me H 1Et-5-Ind C 351 (M⁺ + 1) N-b-28 NA N-b-27 Et H H H1Et-5-Ind C 337 (M⁺ + 1) N-b-29 NB1 Int.n-12 BRA5 Et H Me H 5-1HIdz C324 (M⁺ + 1) N-b-30 NA N-b-29 Et H H H 5-1HIdz C 310 (M⁺ + 1) N-b-31 NB1Int.n-12 BRA6 Et H Me H 1Me-5-1HIdz C 338 (M⁺ + 1) N-b-32 NA N-b-31 Et HH H 1Me-5-1HIdz C 324 (M⁺ + 1) N-b-33 NB1 Int.n-12 BRA7 Et H Me H1Et-5-Idz C 352 (M⁺ + 1) N-b-34 NA N-b-33 Et H H H 1Et-5-Idz C 338(M⁺ + 1) N-b-35 NB1 Int.n-12 BRA8 Et H Me H 2Me-5-Idz C 338 (M⁺ + 1)N-b-36 NA N-b-35 Et H H H 2Me-5-Idz C 324 (M⁺ + 1) N-b-37 NB1 Int.n-12BRA9 Et H Me H 5-Bzt C 341 (M⁺ + 1) N-b-38 NA N-b-37 Et H H H 5-Bzt C327 (M⁺ + 1) N-b-39 NB1 Int.n-12 BRA10 Et H Me H 3-Qu C 335 (M⁺ + 1)N-b-40 NA N-b-39 Et H H H 3-Qu C 321 (M⁺ + 1) N-b-41 NB1 Int.n-12 BRA11Et H Me H 6-Qu C 335 (M⁺ + 1) N-b-42 NA N-b-41 Et H H H 6-Qu C 321(M⁺ + 1) N-b-43 NC2 N-b-21 CHO2 Et Et Me H 2-Nap C 362 (M⁺ + 1) N-b-44NA N-b-43 Et Et H H 2-Nap C 348 (M⁺ + 1)

TABLE N-B-2 LCMS Exp. Syn. SM1 SM2 Rz Ry Y Zx AR method RTime MassN-b-45 NC2 N-b-25 CHO2 Et Et Me H 1Me-5-Ind C 365 (M⁺ + 1) N-b-46 NAN-b-45 Et Et H H 1Me-5-Ind C 351 (M⁺ + 1) N-b-47 NB1 Int.n-13 nPr H Me H5-Ind C 337 (M⁺ + 1) N-b-48 NA N-b-47 nPr H H H 5-Ind C 323 (M⁺ + 1)N-b-49 NB1 Int.n-13 nPr H Me H 1Me-5-Ind C 351 (M⁺ + 1) N-b-50 NA N-b-49nPr H H H 1Me-5-Ind C 337 (M⁺ + 1) N-b-51 NB1 Int.n-13 nPr H Me H5-1HIdz C 338 (M⁺ + 1) N-b-52 NA N-b-51 nPr H H H 5-1HIdz C 324 (M⁺ + 1)N-b-53 NB1 Int.n-13 nPr H Me H 1Me-5-1HIdz C 352 (M⁺ + 1) N-b-54 NAN-b-53 nPr H H H 1Me-5-1HIdz C 338 (M⁺ + 1) N-b-55 NC2 N-b-47 CHO1 nPrMe Me H 5-Ind C 351 (M⁺ + 1) N-b-56 NA N-b-55 nPr Me H H 5-Ind C 337(M⁺ + 1) N-b-57 NC2 N-b-49 CHO1 nPr Me Me H 1Me-5-Ind C 365 (M⁺ + 1)N-b-58 NA N-b-57 nPr Me H H 1Me-5-Ind C 351 (M⁺ + 1) N-b-59 NC2 N-b-51CHO1 nPr Me Me H 5-1HIdz C 352 (M⁺ + 1) N-b-60 NA N-b-59 nPr Me H H5-1HIdz C 338 (M⁺ + 1) N-b-61 NC2 N-b-53 CHO1 nPr Me Me H 1Me-5-1HIdz C366 (M⁺ + 1) N-b-62 NA N-b-61 nPr Me H H 1Me-5-1HIdz C 352 (M⁺ + 1)N-b-63 NB1 Int.n-14 BRA2 iPr H Me H 5-Ind C 337 (M⁺ + 1) N-b-64 NAN-b-63 iPr H H H 5-Ind C 323 (M⁺ + 1) N-b-65 NB1 Int.n-14 BRA3 iPr H MeH 1Me-5-Ind C 351 (M⁺ + 1) N-b-66 NA N-b-65 iPr H H H 1Me-5-Ind C 337(M⁺ + 1) N-b-67 NB1 Int.n-14 BRA5 iPr H Me H 5-1HIdz C 338 (M⁺ + 1)N-b-68 NA N-b-67 iPr H H H 5-1HIdz C 324 (M⁺ + 1) N-b-69 NB1 Int.n-14BRA6 iPr H Me H 1Me-5-1HIdz C 352 (M⁺ + 1) N-b-70 NA N-b-69 iPr H H H1Me-5-1HIdz C 338 (M⁺ + 1) N-b-71 NC2 N-b-63 CHO1 iPr Me Me H 5-Ind C351 (M⁺ + 1) N-b-72 NA N-b-71 iPr Me H H 5-Ind C 337 (M⁺ + 1) N-b-73 NC2N-b-65 CHO1 iPr Me Me H 1Me-5-Ind C 365 (M⁺ + 1) N-b-74 NA N-b-73 iPr MeH H 1Me-5-Ind C 351 (M⁺ + 1) N-b-75 NC1 N-b-67 CHO1 iPr Me Me H 5-1HIdzC 352 (M⁺ + 1) N-b-76 NA N-b-75 iPr Me H H 5-1HIdz C 338 (M⁺ + 1) N-b-77NC1 N-b-69 CHO1 iPr Me Me H 1Me-5-1HIdz C 366 (M⁺ + 1) N-b-78 NA N-b-77iPr Me H H 1Me-5-1HIdz C 352 (M⁺ + 1) N-b-79 NB1 Int.n-7 BRA1 nBu H Me H2-Nap C 362 (M⁺ + 1) N-b-80 NA N-b-79 nBu H H H 2-Nap C 348 (M⁺ + 1)N-b-81 NB1 Int.n-8 BRA2 nBu H Me H 5-Ind C 351 (M⁺ + 1) N-b-82 NA N-b-81nBu H H H 5-Ind C 337 (M⁺ + 1) N-b-83 NB1 Int.n-10 BRA5 nBu H Me H5-1HIdz C 352 (M⁺ + 1) N-b-84 NA N-b-83 nBu H H H 5-1HIdz C 338 (M⁺ + 1)N-b-85 NB1 Int.n-11 BRA6 nBu H Me H 1Me-5-1HIdz C 366 (M⁺ + 1) N-b-86 NAN-b-85 nBu H H H 1Me-5-1HIdz C 352 (M⁺ + 1) N-b-87 NC1 N-b-79 CHO1 nBuMe Me H 2-Nap C 376 (M⁺ + 1) N-b-88 NA N-b-87 nBu Me H H 2-Nap C 351(M⁺ + 1) N-b-89 NC1 N-b-81 CHO1 nBu Me Me H 5-Ind C 365 (M⁺ + 1) N-b-90NA N-b-89 nBu Me H H 5-Ind C 351 (M⁺ + 1)

TABLE N-B-3 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-b-91NC1 N-b-83 CHO1 nBu Me Me H 5-1HIdz C 366 (M⁺ + 1) N-b-92 NA N-b-91 nBuMe H H 5-1HIdz C 352 (M⁺ + 1) N-b-93 NC1 N-b-85 CHO1 nBu Me Me H1Me-5-1HIdz C 380 (M⁺ + 1) N-b-94 NA N-b-93 nBu Me H H 1Me-5-1HIdz C 366(M⁺ + 1) N-b-95 NC2 N-b-81 CHO2 nBu Et Me H 5-Ind C 379 (M⁺ + 1) N-b-96NA N-b-95 nBu Et H H 5-Ind C 365 (M⁺ + 1) N-b-97 NC2 N-b-85 CHO2 nBu EtMe H 1Me-5-1HIdz C 394 (M⁺ + 1) N-b-98 NA N-b-97 nBu Et H H 1Me-5-1HIdzC 380 (M⁺ + 1) N-b-99 NC2 Int.n-9 CHO7 iBu H Me H 1Me-5-Ind C 365(M⁺ + 1) N-b-100 NA N-b-99 iBu H H H 1Me-5-Ind C 351 (M⁺ + 1) N-b-101NC2 Int.n-10 CHO7 iBu H Me H 5-1HIdz C 352 (M⁺ + 1) N-b-102 NA N-b-101iBu H H H 5-1HIdz C 338 (M⁺ + 1) N-b-103 NC2 Int.n-11 CHO7 iBu H Me H1Me-5-1HIdz C 366 (M⁺ + 1) N-b-104 NA N-b-103 iBu H H H 1Me-5-1HIdz C352 (M⁺ + 1) N-b-105 NC2 Int.n-15 BRA11 iBu H Me H 6-Qu C 363 (M⁺ + 1)N-b-106 NA N-b-105 iBu H H H 6-Qu C 349 (M⁺ + 1) N-b-107 NC1 N-b-99 CHO1iBu Me Me H 1Me-5-Ind C 379 (M⁺ + 1) N-b-108 NA N-b-107 iBu Me H H1Me-5-Ind C 365 (M⁺ + 1) N-b-109 NC1 N-b-103 CHO1 iBu Me Me H1Me-5-1HIdz C 380 (M⁺ + 1) N-b-110 NA N-b-109 iBu Me H H 1Me-5-1HIdz C366 (M⁺ + 1) N-b-111 NC1 N-b-105 CHO1 iBu Me Me H 6-Qu C 377 (M⁺ + 1)N-b-112 NA N-b-111 iBu Me H H 6-Qu C 363 (M⁺ + 1) N-b-113 NC2 N-b-99CHO2 iBu Et Me H 1Me-5-Ind C 393 (M⁺ + 1) N-b-114 NA N-b-113 iBu Et H H1Me-5-Ind C 379 (M⁺ + 1) N-b-115 NC2 N-b-101 CHO2 iBu Et Me H 5-1HIdz C380 (M⁺ + 1) N-b-116 NA N-b-115 iBu Et H H 5-1HIdz C 366 (M⁺ + 1)N-b-117 NC2 N-b-103 CHO2 iBu Et Me H 1Me-5-1HIdz C 394 (M⁺ + 1) N-b-118NA N-b-117 iBu Et H H 1Me-5-1HIdz C 380 (M⁺ + 1) N-b-119 NB1 Int.n-16BRA1 cPen H Me H 2-Nap C 374 (M⁺ + 1) N-b-120 NA N-b-119 cPen H H H2-Nap C 360 (M⁺ + 1) N-b-121 NB1 Int.n-16 BRA2 cPen H Me H 5-Ind C 363(M⁺ + 1) N-b-122 NA N-b-121 cPen H H H 5-Ind C 349 (M⁺ + 1) N-b-123 NB1Int.n-9 BRA3 cPen H Me H 1Me-5-Ind C 377 (M⁺ + 1) N-b-124 NA N-b-123cPen H H H 1Me-5-Ind C 363 (M⁺ + 1) N-b-125 NB1 Int.n-16 BRA5 cPen H MeH 5-1HIdz C 364 (M⁺ + 1) N-b-126 NA N-b-125 cPen H H H 5-1HIdz C 350(M⁺ + 1) N-b-127 NB1 Int.n-11 BRA6 cPen H Me H 1Me-5-1HIdz C 378(M⁺ + 1) N-b-128 NA N-b-127 cPen H H H 1Me-5-1HIdz C 364 (M⁺ + 1)N-b-129 NB1 Int.n-16 BRA11 cPen H Me H 6-Qu C 375 (M⁺ + 1) N-b-130 NAN-b-129 cPen H H H 6-Qu C 361 (M⁺ + 1) N-b-131 NB1 Int.n-16 BRA9 cPen HMe H 5-Bzt C 381 (M⁺ + 1) N-b-132 NA N-b-131 cPen H H H 5-Bzt C 367(M⁺ + 1) N-b-133 NC1 N-b-121 CHO1 cPen Me Me H 5-Ind C 377 (M⁺ + 1)N-b-134 NA N-b-133 cPen Me H H 5-Ind C 363 (M⁺ + 1) N-b-135 NC1 N-b-123CHO1 cPen Me Me H 1Me-5-Ind C 391 (M⁺ + 1) N-b-136 NA N-b-135 cPen Me HH 1Me-5-Ind C 377 (M⁺ + 1)

TABLE N-B-4 LCMS Exp. Syn. SM1 SM2 Rz Ry Y Zx AR method RTime MassN-b-137 NC1 N-b-127 CHO1 cPen Me Me H 1Me-5-1HIdz C 392 (M⁺ + 1) N-b-138NA N-b-137 cPen Me H H 1Me-5-1HIdz C 378 (M⁺ + 1) N-b-139 NC2 N-b-123CHO2 cPen Et Me H 1Me-5-Ind C 405 (M⁺ + 1) N-b-140 NA N-b-139 cPen Et HH 1Me-5-Ind C 391 (M⁺ + 1) N-b-141 NC2 N-b-131 CHO2 cPen Et Me H 5-Bzt C409 (M⁺ + 1) N-b-142 NA N-b-141 cPen Et H H 5-Bzt C 395 (M⁺ + 1) N-b-143NB1 Int.n-17 BRA1 cHex H Me H 2-Nap C 388 (M⁺ + 1) N-b-144 NA N-b-143cHex H H H 2-Nap C 374 (M⁺ + 1) N-b-145 NB1 Int.n-17 BRA2 cHex H Me H5-Ind C 377 (M⁺ + 1) N-b-146 NA N-b-145 cHex H H H 5-Ind C 363 (M⁺ + 1)N-b-147 NB1 Int.n-9 BRA3 cHex H Me H 1Me-5-Ind C 391 (M⁺ + 1) N-b-148 NAN-b-147 cHex H H H 1Me-5-Ind C 377 (M⁺ + 1) N-b-149 NB1 Int.n-17 BRA5cHex H Me H 5-1HIdz C 378 (M⁺ + 1) N-b-150 NA N-b-149 cHex H H H 5-1HIdzC 364 (M⁺ + 1) N-b-151 NB1 Int.n-17 BRA6 cHex H Me H 1Me-5-1HIdz C 392(M⁺ + 1) N-b-152 NA N-b-151 cHex H H H 1Me-5-1HIdz C 378 (M⁺ + 1)N-b-153 NB1 Int.n-17 BRA10 cHex H Me H 3-Qu C 389 (M⁺ + 1) N-b-154 NAN-b-153 cHex H H H 3-Qu C 375 (M⁺ + 1) N-b-155 NC1 N-b-143 CHO1 cHex MeMe H 2-Nap C 402 (M⁺ + 1) N-b-156 NA N-b-155 cHex Me H H 2-Nap C 388(M⁺ + 1) N-b-157 NC1 N-b-147 CHO1 cHex Me Me H 1Me-5-Ind C 405 (M⁺ + 1)N-b-158 NA N-b-157 cHex Me H H 1Me-5-Ind C 391 (M⁺ + 1) N-b-159 NC1N-b-149 CHO1 cHex Me Me H 5-1HIdz C 392 (M⁺ + 1) N-b-160 NA N-b-159 cHexMe H H 5-1HIdz C 378 (M⁺ + 1) N-b-161 NC1 N-b-151 CHO1 cHex Me Me H1Me-5-1HIdz C 406 (M⁺ + 1) N-b-162 NA N-b-161 cHex Me H H 1Me-5-1HIdz C392 (M⁺ + 1) N-b-163 NC2 N-b-143 CHO2 cHex Et Me H 2-Nap C 416 (M⁺ + 1)N-b-164 NA N-b-163 cHex Et H H 2-Nap C 402 (M⁺ + 1) N-b-165 NC2 N-b-153CHO2 cHex Et Me H 3-Qu C 417 (M⁺ + 1) N-b-166 NA N-b-165 cHex Et H H3-Qu C 403 (M⁺ + 1) N-b-167 NB1 Int.n-18 BRA2 2(Me)cHex H Me H 5-Ind C391 (M⁺ + 1) N-b-168 NA N-b-167 2(Me)cHex H H H 5-Ind C 377 (M⁺ + 1)N-b-169 NB1 Int.n-18 BRA3 2(Me)cHex H Me H 1Me-5-Ind C 405 (M⁺ + 1)N-b-170 NA N-b-169 2(Me)cHex H H H 1Me-5-Ind C 391 (M⁺ + 1) N-b-171 NB1Int.n-18 BRA5 2(Me)cHex H Me H 5-1HIdz C 392 (M⁺ + 1) N-b-172 NA N-b-1712(Me)cHex H H H 5-1HIdz C 378 (M⁺ + 1) N-b-173 NB1 Int.n-18 BRA62(Me)cHex H Me H 1Me-5-1HIdz C 406 (M⁺ + 1) N-b-174 NA N-b-173 2(Me)cHexH H H 1Me-5-1HIdz C 392 (M⁺ + 1) N-b-175 NC2 Int.n-8 CHO25 2-Indane H MeH 5-Ind C 411 (M⁺ + 1) N-b-176 NA N-b-175 2-Indane H H H 5-Ind C 397(M⁺ + 1) N-b-177 NC2 Int.n-9 CHO25 2-Indane H Me H 1Me-5-Ind C 425(M⁺ + 1) N-b-178 NA N-b-177 2-Indane H H H 1Me-5-Ind C 411 (M⁺ + 1)N-b-179 NC2 Int.n-10 CHO25 2-Indane H Me H 5-1HIdz C 412 (M⁺ + 1)N-b-180 NA N-b-179 2-Indane H H H 5-1HIdz C 398 (M⁺ + 1) N-b-181 NC2Int.n-11 CHO25 2-Indane H Me H 1Me-5-1HIdz C 426 (M⁺ + 1) N-b-182 NAN-b-181 2-Indane H H H 1Me-5-1HIdz C 412 (M⁺ + 1)

TABLE-N-B-5 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-b-183 NF N-b-1 AcCl Me Ac Me H 2-Nap C 364 (M⁺ + 1) N-b-184 NA N-b-183Me Ac H H 2-Nap C 350 (M⁺ + 1) N-b-185 NF N-b-5 AcCl Me Ac Me H1Me-5-Ind C 367 (M⁺ + 1) N-b-186 NA N-b-185 Me Ac H H 1Me-5-Ind C 353(M⁺ + 1) N-b-187 NF N-b-11 AcCl Me Ac Me H 1Me-5-1HIdz C 368 (M⁺ + 1)N-b-188 NA N-b-187 Me Ac H H 1Me-5-1HIdz C 354 (M⁺ + 1) N-b-189 NFInt.n-11 AcCl Ac Ac Me H 1Me-5-1HIdz C 394 (M⁺ + 1) N-b-190 NA N-b-189Ac Ac H H 1Me-5-1HIdz C 380 (M⁺ + 1) N-b-191 NF Int.n-18 MeOCOCl MeMeOC(O) Me H 2-Nap C 380 (M⁺ + 1) N-b-192 NA N-b-167 Me MeOC(O) H H2-Nap C 366 (M⁺ + 1) N-b-193 NF Int.n-18 MeOCOCl Me MeOC(O) Me H1Me-5-Ind C 383 (M⁺ + 1) N-b-194 NA N-b-169 Me MeOC(O) H H 1Me-5-Ind C369 (M⁺ + 1) N-b-195 NF Int.n-18 MeOCOCl Me MeOC(O) Me H 1Me-5-1HIdz C384 (M⁺ + 1) N-b-196 NA N-b-171 Me MeOC(O) H H 1Me-5-1HIdz C 370(M⁺ + 1) N-b-197 NF-NA N-b-1 BzCl Me Bz H H 2-Nap C 396 (M⁺ + 1) N-b-198NF-NA N-b-3 BzCl Me Bz H H 5-Ind C 399 (M⁺ + 1) N-b-199 NF-NA N-b-5 BzClMe Bz H H 1Me-5-Ind C 399 (M⁺ + 1) N-b-200 NF-NA N-b-9 BzCl Me Bz H H5-1HIdz C 386 (M⁺ + 1) N-b-201 NF-NA N-b-11 BzCl Me Bz H H 1Me-5-1HIdz C400 (M⁺ + 1) N-b-202 NF-NA N-b-1 PhOCOCl Me

H H 2-Nap C 412 (M⁺ + 1) N-b-203 NF-NA N-b-5 PhOCOCl Me

H H 1Me-5-Ind C 415 (M⁺ + 1) N-b-204 NF-NA N-b-1 cPenCH2COCl Me

H H 2-Nap C 402 (M⁺ + 1) N-b-205 NF-NA N-b-3 cPenCH2COCl Me

H H 1Me-5-Ind C 405 (M⁺ + 1) N-b-206 NF-NA N-b-1

Me

H H 2-Nap C 403 (M⁺ + 1) N-b-207 NF-NA N-b-5

Me

H H 1Me-5-Ind C 406 (M⁺ + 1) N-b-208 NF-NA N-b-1 PhNCO Me PhNHC(O) H H2-Nap C 411 (M⁺ + 1) N-b-209 NF-NA N-b-5 PhNCO Me PhNHC(O) H H 1Me-5-IndC 414 (M⁺ + 1) N-b-210 NF-NA N-b-1 cHexNCO Me chexNHC(O) H H 2-Nap C 417(M⁺ + 1) N-b-211 NF-NA N-b-5 cHexNCO Me cHexNHC(O) H H 1Me-5-Ind C 420(M⁺ + 1) N-b-212 NF-NA N-b-1 cHexNCS Me PhNHC(S) H H 2-Nap C 430 (M⁺ +1)

Example N-c-51 Synthesis of ethyl3-[4-(imidazol-1-yl)-3-(naphthalen-2-yl)phenyl]acrylate (Compound No.N-c-51) (Synthesis method NB1)

According to the procedure described in the synthesis method of thecompound of Example N-a-1 (Synthesis method NB1) provided that thereaction was carried out for 16 hours, and the column chromatography wasperformed with chloroform:methanol=100:1, Intermediate n-33 (300.4 mg),2-naphthaleneboronic acid (208.3 mg), 2 M aqueous sodium carbonate (900μl) and (Ph₃P)₄Pd (108.3 mg) were reacted and treated to obtain thetitle compound (Intermediate N-c-51, 304.2 mg).

Example N-c-52 Synthesis of3-[4-(imidazol-1-yl)-3-(naphthalen-2-yl)phenyl]acrylic acid (CompoundNo. N-c-51) (Synthesis method NA)

According to the procedure described in the synthesis method of thecompound of Example N-a-2 (Synthesis method NA) provided that thereaction was carried out for 2 hours, the compound of Example N-c-51(301.2 mg) and 2 N aqueous sodium hydroxide (980 μl) were reacted andtreated to obtain the title compound (Compound No. N-c-52, 286.4 mg).

Examples N-c-1 to N-c-64

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-N-C-1 to Table-N-C-3. In thetables, the compound numbers are mentioned in the columns indicated as“Exp.”. In the tables, used methods among the aforementioned synthesismethods are shown in the columns of “Syn” with symbols, the startingcompounds 1 are mentioned in the columns of “SM1”, and the startingcompounds 2 are mentioned in the columns of “SM2”.

TABLE-N-C-1

LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-c-1 NB1 Int.n-36BRA1

Me H 2-Nap C 358 (M⁺ + 1) N-c-2 NA N-c-1

H H 2-Nap C 344 (M⁺ + 1) N-c-3 NB1 Int.n-36 BRA2

Me H 5-Ind C 347 (M⁺ + 1) N-c-4 NA N-c-3

H H 5-Ind C 333 (M⁺ + 1) N-c-5 NB1 Int.n-36 BRA3

Me H 1Me-5-Ind C 361 (M⁺ + 1) N-c-6 NA N-c-5

H H 1Me-5-Ind C 347 (M⁺ + 1) N-c-7 NB1 Int.n-36 BRA5

Me H 5-1HIdz C 348 (M⁺ + 1) N-c-8 NA N-c-7

H H 5-1HIdz C 334 (M⁺ + 1) N-c-9 NB1 Int.n-36 BRA6

Me H 1Me-5-1HIdz C 362 (M⁺ + 1) N-c-10 NA N-c-9

H H 1Me-5-1HIdz C 348 (M⁺ + 1) N-c-11 NB1 Int.n-36 BRA9

Me H 5-Bzt C 365 (M⁺ + 1) N-c-12 NA N-c-11

H H 5-Bzt C 351 (M⁺ + 1) N-c-13 NB1 Int.n-36 BRA10

Me H 3-Qu C 359 (M⁺ + 1) N-c-14 NA N-c-13

H H 3-Qu C 345 (M⁺ + 1) N-c-15 NB1 Int.n-36 BRA11

Me H 6-Qu C 359 (M⁺ + 1) N-c-16 NA N-c-15

H H 6-Qu C 345 (M⁺ + 1) N-c-17 NB1 Int.n-37 BRA1

Me H 2-Nap C 374 (M⁺ + 1) N-c-18 NA N-c-17

H H 2-Nap C 360 (M⁺ + 1) N-c-19 NB1 Int.n-37 BRA2

Me H 5-Ind C 363 (M⁺ + 1) N-c-20 NA N-c-19

H H 5-Ind C 349 (M⁺ + 1) N-c-21 NB1 Int.n-37 BRA3

Me H 1Me-5-Ind C 377 (M⁺ + 1) N-c-22 NA N-c-21

H H 1me-5-Ind C 363 (M⁺ + 1)

TABLE-N-C-2 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-c-23NB1 Int.n-37 BRA5

Me H 5-1HIdz C 364 (M⁺ + 1) N-c-24 NA N-c-23

H H 5-1HIdz C 350 (M⁺ + 1) N-c-25 NB1 Int.n-37 BRA6

Me H 1Me-5-1HIdz C 378 (M⁺ + 1) N-c-26 NA N-c-25

H H 1Me-5-1HIdz C 364 (M⁺ + 1) N-c-27 NB1 Int.n-26 BRA1

Me H 2-Nap C 372 (M⁺ + 1) N-c-28 NA N-c-27

H H 2-Nap C 358 (M⁺ + 1) N-c-29 NB1 Int.n-26 BRA2

Me H 5-Ind C 361 (M⁺ + 1) N-c-30 NA N-c-29

H H 5-Ind C 347 (M⁺ + 1) N-c-31 NB1 Int.n-26 BRA3

Me H 1Me-5-Ind C 375 (M⁺ + 1) N-c-32 NA N-c-31

H H 1Me-5-Ind C 361 (M⁺ + 1) N-c-33 NB1 Int.n-26 BRA5

Me H 5-1HIdz C 362 (M⁺ + 1) N-c-34 NA N-c-33

H H 5-1HIdz C 348 (M⁺ + 1) N-c-35 NB1 Int.n-26 BRA6

Me H 1Me-5-1HIdz C 376 (M⁺ + 1) N-c-36 NA N-c-35

H H 1Me-5-1HIdz C 362 (M⁺ + 1) N-c-37 NB1 Int.n-28 BRA1

Me H 2-Nap C 386 (M⁺ + 1) N-c-38 NA N-c-37

H H 2-Nap C 372 (M⁺ + 1) N-c-39 NB1 Int.n-28 BRA3

Me H 1Me-5-Ind C 389 (M⁺ + 1) N-c-40 NA N-c-39

H H 1Me-5-Ind C 375 (M⁺ + 1) N-c-41 NB1 Int.n-28 BRA5

Me H 5-1HIdz C 376 (M⁺ + 1) N-c-42 NA N-c-41

H H 5-1HIdz C 362 (M⁺ + 1) N-c-43 NB1 Int.n-28 BRA6

Me H 1Me-5-1HIdz C 390 (M⁺ + 1) N-c-44 NA N-c-43

H H 1Me-5-1HIdz C 376 (M⁺ + 1)

TABLE-N-C-3 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-c-45NB1 Int.n-30 BRA3

Me H 1Me-5-Ind C 389 (M⁺ + 1) N-c-46 NA N-c-45

H H 1Me-5-Ind C 375 (M⁺ + 1) N-c-47 NB1 Int.n-30 BRA5

Me H 5-1HIdz C 376 (M⁺ + 1) N-c-48 NA N-c-47

H H 5-1HIdz C 362 (M⁺ + 1) N-c-49 NB1 Int.n-30 BRA6

Me H 1Me-5-1HIdz C 390 (M⁺ + 1) N-c-50 NA N-c-49

H H 1Me-5-1HIdz C 376 (M⁺ + 1) N-c-51 NB1 Int.n-33 BRA1

Et H 2-Nap C 369 (M⁺ + 1) N-c-52 NA N-c-51

H H 2-Nap C 341 (M⁺ + 1) N-c-53 NB1 Int.n-33 BRA3

Et H 1Me-5-Ind C 372 (M⁺ + 1) N-c-54 NA N-c-53

H H 1Me-5-Ind C 344 (M⁺ + 1) N-c-55 NB1 Int.n-33 BRA6

Et H 1Me-5-1HIdz C 373 (M⁺ + 1) N-c-56 NA N-c-55

H H 1Me-5-1HIdz C 345 (M⁺ + 1) N-c-57 NB1 Int.n-35 BRA1

Et H 2-Nap C 368 (M⁺ + 1) N-c-58 NA N-c-57

H H 2-Nap C 340 (M⁺ + 1) N-c-59 NB1 Int.n-35 BRA3

Et H 1Me-5-Ind C 371 (M⁺ + 1) N-c-60 NA N-c-59

H H 1Me-5-Ind C 343 (M⁺ + 1) N-c-61 NB1 Int.n-35 BRA5

Et H 5-1HIdz C 358 (M⁺ + 1) N-c-62 NA N-c-61

H H 5-1HIdz C 330 (M⁺ + 1) N-c-63 NB1 Int.n-35 BRA6

Et H 1Me-5-1HIdz C 372 (M⁺ + 1) N-c-64 NA N-c-63

H H 1Me-5-1HIdz C 344 (M⁺ + 1)

Example N-d-61 Synthesis of ethyl3-[4-(imidazol-1-yl)-3-(naphthalen-2-yl)phenyl]propionate (Compound No.N-d-51) (Synthesis method ND1)

According to the procedure described in the synthesis method ofIntermediate n-7 (Synthesis method ND1) provided that the reaction wascarried out for 6 hours, the compound of Example N-c-51 (301.5 mg) and10% palladium/carbon (67.3 mg) were reacted and treated to obtain thetitle compound (Compound No. N-d-61, 143.5 mg).

Example N-d-62 Synthesis of3-[4-(imidazol-1-yl)-3-(naphthalen-2-yl)phenyl]propionic acid (CompoundNo. N-d-62) (Synthesis method NA)

According to the procedure described in the synthesis method of thecompound of Example N-a-2 (Synthesis method NA) provided that thereaction was carried out for 3 hours, the compound of Example N-d-61(140.3 mg) and 2 N aqueous sodium hydroxide (600 μl) were reacted andtreated to obtain the title compound (Compound No. N-d-62, 100.4 mg).

Examples N-d-1 to N-d-74

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-N-D-1 to Table-N-D-4. In thetables, the compound numbers are mentioned in the columns indicated as“Exp.”. In the tables, used methods among the aforementioned synthesismethods are shown in the columns of “Syn” with symbols, the startingcompounds 1 are mentioned in the columns of “SM1”, and the startingcompounds 2 are mentioned in the columns of “SM2”.

TABLE-N-D-1

LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-d-1 NB1 Int.n-21BRA1

Me H 2-Nap C 360 (M⁺ + 1) N-d-2 NA N-d-1

H H 2-Nap C 346 (M⁺ + 1) N-d-3 NB1 Int.n-21 BRA2

Me H 5-Ind D 4.79 349 (M⁺ + 1) N-d-4 NA N-d-3

H H 5-Ind D 3.54 335 (M⁺ + 1) N-d-5 NB1 Int.n-21 BRA3

Me H 1Me-5-Ind D 5.72 363 (M⁺ + 1) N-d-6 NA N-d-5

H H 1Me-5-Ind D 4.31 349 (M⁺ + 1) N-d-7 NB1 Int.n-21 BRA5

Me H 5-1HIdz C 350 (M⁺ + 1) N-d-8 NA N-d-7

H H 5-1HIdz C 336 (M⁺ + 1) N-d-9 NB1 Int.n-21 BRA6

Me H 1Me-5-1HIdz C 364 (M⁺ + 1) N-d-10 NA N-d-9

H H 1Me-5-1HIdz C 350 (M⁺ + 1) N-d-11 NB1 Int.n-21 BRA9

Me H 5-Bzt C 367 (M⁺ + 1) N-d-12 NA N-d-11

H H 5-Bzt C 353 (M⁺ + 1) N-d-13 NB1 Int.n-21 BRA10

Me H 3-Qu C 361 (M⁺ + 1) N-d-14 NA N-d-13

H H 3-Qu C 347 (M⁺ + 1) N-d-15 NB1 Int.n-21 BRA11

Me H 6-Qu C 361 (M⁺ + 1) N-d-16 NA N-d-15

H H 6-Qu C 347 (M⁺ + 1) N-d-17 NB1 Int.n-24 BRA1

Me H 2-Nap C 376 (M⁺ + 1) N-d-18 NA N-d-17

H H 2-Nap C 362 (M⁺ + 1) N-d-19 NB1 Int.n-24 BRA2

Me H 5-Ind C 365 (M⁺ + 1) N-d-20 NA N-d-19

H H 5-Ind C 351 (M⁺ + 1) N-d-21 NB1 Int.n-24 BRA3

Me H 1Me-5-Ind C 379 (M⁺ + 1) N-d-22 NA N-d-21

H H 1Me-5-Ind C 365 (M⁺ + 1)

TABLE-N-D-2 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-d-23NB1 Int.n-24 BRA5

Me H 5-1HIdz C 366 (M⁺ + 1) N-d-24 NA N-d-23

H H 5-1HIdz C 352 (M⁺ + 1) N-d-25 NB1 Int.n-24 BRA6

Me H 1Me-5-1HIdz C 380 (M⁺ + 1) N-d-26 NA N-d-25

H H 1Me-5-1HIdz C 366 (M⁺ + 1) N-d-27 NB1 Int.n-24 BRA9

Me H 5-Bzt C 383 (M⁺ + 1) N-d-28 NA N-d-27

H H 5-Bzt C 369 (M⁺ + 1) N-d-29 NB1 Int.n-24 BRA11

Me H 6-Qu C 377 (M⁺ + 1) N-d-30 NA N-d-29

H H 6-Qu C 363 (M⁺ + 1) N-d-31 NB1 Int.n-27 BRA1

Me H 2-Nap C 374 (M⁺ + 1) N-d-32 NA N-d-31

H H 2-Nap C 360 (M⁺ + 1) N-d-33 NB1 Int.n-27 BRA2

Me H 5-Ind C 363 (M⁺ + 1) N-d-34 NA N-d-33

H H 5-Ind C 349 (M⁺ + 1) N-d-35 NB1 Int.n-27 BRA3

Me H 1Me-5-Ind C 377 (M⁺ + 1) N-d-36 NA N-d-35

H H 1Me-5-Ind C 363 (M⁺ + 1) N-d-37 NB1 Int.n-27 BRA5

Me H 5-1HIdz C 364 (M⁺ + 1) N-d-38 NA N-d-37

H H 5-1HIdz C 350 (M⁺ + 1) N-d-39 NB1 Int.n-27 BRA6

Me H 1Me-5-1HIdz C 378 (M⁺ + 1) N-d-40 NA N-d-39

H H 1Me-5-1HIdz C 364 (M⁺ + 1) N-d-41 NB1 Int.n-27 BRA11

Me H 6-Qu C 375 (M⁺ + 1) N-d-42 NA N-d-41

H H 6-Qu C 361 (M⁺ + 1) N-d-43 NB1 Int.n-27 BRA9

Me H 5-Bzt C 381 (M⁺ + 1) N-d-44 NA N-d-43

H H 5-Bzt C 367 (M⁺ + 1)

TABLE-N-D-3 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-d-45NB1 Int.n-29 BRA1

Me H 2-Nap C 388 (M⁺ + 1) N-d-46 NA N-d-45

H H 2-Nap C 374 (M⁺ + 1) N-d-47 NB1 Int.n-29 BRA3

Me H 1Me-5-Ind C 391 (M⁺ + 1) N-d-48 NA N-d-47

H H 1Me-5-Ind C 377 (M⁺ + 1) N-d-49 NB1 Int.n-29 BRA5

Me H 5-1Idz C 378 (M⁺ + 1) N-d-50 NA N-d-49

H H 5-1Idz C 364 (M⁺ + 1) N-d-51 NB1 Int.n-29 BRA6

Me H 1Me-5-1HIdz C 392 (M⁺ + 1) N-d-52 NA N-d-51

H H 1Me-5-1HIdz C 378 (M⁺ + 1) N-d-53 NB1 Int.n-29 BRA10

Me H 3-Qu C 389 (M⁺ + 1) N-d-54 NA N-d-53

H H 3-Qu C 375 (M⁺ + 1) N-d-55 NB1 Int.n-31 BRA3

Me H 1Me-5-Ind C 391 (M⁺ + 1) N-d-56 NA N-d-55

H H 1Me-5-Ind C 377 (M⁺ + 1) N-d-57 NB1 Int.n-31 BRA5

Me H 5-1Idz C 378 (M⁺ + 1) N-d-58 NA N-d-57

H H 5-1Idz C 364 (M⁺ + 1) N-d-59 NB1 Int.n-31 BRA6

Me H 1Me-5-1HIdz C 392 (M⁺ + 1) N-d-60 NA N-d-59

H H 1Me-5-1HIdz C 378 (M⁺ + 1) N-d-61 ND1 N-c-51

Et H 2-Nap C 371 (M⁺ + 1) N-d-62 NA N-d-61

H H 2-Nap C 343 (M⁺ + 1) N-d-63 ND1 N-c-53

Et H 1Me-5-Ind C 374 (M⁺ + 1) N-d-64 NA N-d-63

H H 1Me-5-Ind C 346 (M⁺ + 1) N-d-65 ND1 N-c-55

Et H 1Me-5-1HIdz C 375 (M⁺ + 1) N-d-66 NA N-d-65

H H 1Me-5-1HIdz C 347 (M⁺ + 1)

TABLE-N-D-4 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-d-67ND1 N-c-57

Et H 2-Nap C 370 (M⁺ + 1) N-d-68 NA N-d-45

H H 2-Nap C 342 (M⁺ + 1) N-d-69 ND1 N-c-59

Et H 1Me-5-Ind C 373 (M⁺ + 1) N-d-70 NA N-d-47

H H 1Me-5-Ind C 345 (M⁺ + 1) N-d-71 ND1 N-c-61

Et H 5-1Idz C 360 (M⁺ + 1) N-d-72 NA N-d-49

H H 5-1Idz C 332 (M⁺ + 1) N-d-73 ND1 N-c-63

Et H 1Me-5-1HIdz C 374 (M⁺ + 1) N-d-74 NA N-d-51

H H 1Me-5-1HIdz C 346 (M⁺ + 1)

Examples N-e-1 to N-e-204

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification are shown inTable-N-E-1 to Table-N-E-7. In the tables, the compound numbers arementioned in the columns indicated as “Exp.”. In the tables,corresponding methods among the aforementioned synthesis methods areshown in the columns of “Syn” with symbols, the starting compounds 1 arementioned in the columns of “SM1”, and the starting compounds 2 arementioned in the columns of “SM2”.

TABLE-N-E-1

LCMS Exp. Syn SM1 SM2 NRzRy Y AR method RTime Mass N-e-1 NB1 Int.n-48BRA1

Et 2-Nap C 389 (M⁺ + 1) N-e-2 NA N-e-1

H 2-Nap C 375 (M⁺ + 1) N-e-3 NB1 Int.n-48 BRA2

Et 5-Ind C 378 (M⁺ + 1) N-e-4 NA N-e-3

H 5-Ind C 364 (M⁺ + 1) N-e-5 NB1 Int.n-48 BRA3

Et 1Me-5-Ind C 392 (M⁺ + 1) N-e-6 NA N-e-5

H 1Me-5-Ind C 378 (M⁺ + 1) N-e-7 NB1 Int.n-48 BRA5

Et 5-1HIdz C 379 (M⁺ + 1) N-e-8 NA N-e-7

H 5-1HIdz C 365 (M⁺ + 1) N-e-9 NB1 Int.n-48 BRA6

Et 1Me-5-1HIdz C 393 (M⁺ + 1) N-e-10 NA N-e-9

H 1Me-5-1HIdz C 379 (M⁺ + 1) N-e-11 NB1 Int.n-48 BRA10

Et 3-Qu C 390 (M⁺ + 1) N-e-12 NA N-e-11

H 3-Qu C 376 (M⁺ + 1) N-e-13 NB1 Int.n-48 BRA11

Et 6-Qu C 390 (M⁺ + 1) N-e-14 NA N-e-13

H 6-Qu C 376 (M⁺ + 1) N-e-15 NB1 Int.n-48 BRA12

Et 6-IQ C 390 (M⁺ + 1) N-e-16 NA N-e-15

H 6-IQ C 376 (M⁺ + 1) N-e-17 NB1 Int.n-49 BRA1

Et 2Nap C 375 (M⁺ + 1) N-e-18 NA N-e-17

H 2Nap C 361 (M⁺ + 1) N-e-19 NB1 Int.n-49 BRA2

Et 5-Ind C 364 (M⁺ + 1) N-e-20 NA N-e-19

H 5-Ind C 350 (M⁺ + 1) N-e-21 NB1 Int.n-49 BRA3

Et 1Me-5-Ind C 378 (M⁺ + 1) N-e-22 NA N-e-21

H 1Me-5-Ind C 364 (M⁺ + 1)

TABLE-N-E-2 LCMS Exp. Syn SM1 SM2 NRzRy Y AR method RTime Mass N-e-23NB1 Int.n-49 BRA5

Et 5-1HIdz C 365 (M⁺ + 1) N-e-24 NA N-e-23

H 5-1HIdz C 351 (M⁺ + 1) N-e-25 NB1 Int.n-49 BRA6

Et 1Me-5-1HIdz C 379 (M⁺ + 1) N-e-26 NA N-e-25

H 1Me-5-1HIdz C 365 (M⁺ + 1) N-e-27 NB1 Int.n-50 BRA1

Et 2-Nap C 403 (M⁺ + 1) N-e-28 NA N-e-27

H 2-Nap C 389 (M⁺ + 1) N-e-29 NB1 Int.n-50 BRA2

Et 5-Ind C 392 (M⁺ + 1) N-e-30 NA N-e-29

H 5-Ind C 378 (M⁺ + 1) N-e-31 NB1 Int.n-50 BRA3

Et 1Me-5-Ind C 406 (M⁺ + 1) N-e-32 NA N-e-31

H 1Me-5-Ind C 392 (M⁺ + 1) N-e-33 NB1 Int.n-50 BRA5

Et 5-1HIdz C 393 (M⁺ + 1) N-e-34 NA N-e-33

H 5-1HIdz C 379 (M⁺ + 1) N-e-35 NB1 Int.n-50 BRA6

Et 1Me-5-1HIdz C 407 (M⁺ + 1) N-e-36 NA N-e-35

H 1Me-5-1HIdz C 393 (M⁺ + 1) N-e-37 NB1 Int.n-51 BRA1

Et 2-Nap C 391 (M⁺ + 1) N-e-38 NA N-e-37

H 2-Nap C 377 (M⁺ + 1) N-e-39 NB1 Int.n-51 BRA3

Et 1Me-5-Ind C 394 (M⁺ + 1) N-e-40 NA N-e-39

H 1Me-5-Ind C 380 (M⁺ + 1) N-e-41 NB1 Int.n-51 BRA5

Et 5-1HIdz C 381 (M⁺ + 1) N-e-42 NA N-e-41

H 5-1HIdz C 367 (M⁺ + 1) N-e-43 NB1 Int.n-51 BRA6

Et 1Me-5-1HIdz C 395 (M⁺ + 1) N-e-44 NA N-e-43

H 1Me-5-1HIdz C 381 (M⁺ + 1)

TABLE-N-E-3 LCMS Exp. Syn SM1 SM2 NRzRy Y AR method RTime Mass N-e-45NB1 Int.n-52 BRA1

Et 2-NAP C 403 (M⁺ + 1) N-e-46 NA N-e-45

H 2-NAP C 389 (M⁺ + 1) N-e-47 NB1 Int.n-52 BRA3

Et 1Me-5-Ind C 406 (M⁺ + 1) N-e-48 NA N-e-47

H 1Me-5-Ind C 392 (M⁺ + 1) N-e-49 NB1 Int.n-52 BRA5

Et 5-1HIdz C 393 (M⁺ + 1) N-e-50 NA N-e-49

H 5-1HIdz C 379 (M⁺ + 1) N-e-51 NB1 Int.n-52 BRA6

Et 1Me-5-1HIdz C 407 (M⁺ + 1) N-e-52 NA N-e-51

H 1Me-5-1HIdz C 393 (M⁺ + 1)

TABLE-N-E-4

LCMS Exp. Syn SM1 SM2 Rz Ry Y AR method RTime Mass N-e-53 NB1 Int.n-53BRA1 Et Me Et 2-Nap C 363 (M⁺ + 1) N-e-54 NA N-e-53 Et Me H 2-Nap C 335(M⁺ + 1) N-e-55 NB1 Int.n-53 BRA2 Et Me Et 5-Ind C 352 (M⁺ + 1) N-e-56NA N-e-55 Et Me H 5-Ind C 324 (M⁺ + 1) N-e-57 NB1 Int.n-53 BRA3 Et Me Et1Me-5-Ind C 366 (M⁺ + 1) N-e-58 NA N-e-57 Et Me H 1Me-5-Ind C 338(M⁺ + 1) N-e-59 NB1 Int.n-53 BRA5 Et Me Et 5-1HIdz C 353 (M⁺ + 1) N-e-60NA N-e-59 Et Me H 5-1HIdz C 325 (M⁺ + 1) N-e-61 NB1 Int.n-53 BRA6 Et MeEt 1Me-5-1HIdz C 367 (M⁺ + 1) N-e-62 NA N-e-61 Et Me H 1Me-5-1HIdz C 339(M⁺ + 1) N-e-63 NB1 Int.n-54 BRA1 Et Et Et 2-Nap C 377 (M⁺ + 1) N-e-64NA N-b-63 Et Et H 2-Nap C 349 (M⁺ + 1) N-e-65 NB1 Int.n-54 BRA2 Et Et Et5-Ind C 366 (M⁺ + 1) N-e-66 NA N-b-65 Et Et H 5-Ind C 338 (M⁺ + 1)N-e-67 NB1 Int.n-54 BRA3 Et Et Et 1Me-5-Ind C 380 (M⁺ + 1) N-e-68 NAN-b-67 Et Et H 1Me-5-Ind C 352 (M⁺ + 1) N-e-69 NB1 Int.n-54 BRA5 Et EtEt 5-1HIdz C 367 (M⁺ + 1) N-e-70 NA N-b-69 Et Et H 5-1HIdz C 339(M⁺ + 1) N-e-71 NB1 Int.n-54 BRA6 Et Et Et 1Me-5-1HIdz C 381 (M⁺ + 1)N-e-72 NA N-b-71 Et Et H 1Me-5-1HIdz C 353 (M⁺ + 1) N-e-73 NB1 Int.n-55BRA1 nPr Me Et 2-Nap C 377 (M⁺ + 1) N-e-74 NA N-b-73 nPr Me H 2-Nap C349 (M⁺ + 1) N-e-75 NB1 Int.n-55 BRA2 nPr Me Et 5-Ind C 366 (M⁺ + 1)N-e-76 NA N-b-75 nPr Me H 5-Ind C 338 (M⁺ + 1) N-e-77 NB1 Int.n-55 BRA3nPr Me Et 1Me-5-Ind C 380 (M⁺ + 1) N-e-78 NA N-b-77 nPr Me H 1Me-5-Ind C352 (M⁺ + 1) N-e-79 NB1 Int.n-55 BRA5 nPr Me Et 5-1HIdz C 367 (M⁺ + 1)N-e-80 NA N-b-79 nPr Me H 5-1HIdz C 339 (M⁺ + 1) N-e-81 NB1 Int.n-55BRA6 nPr Me Et 1Me-5-1HIdz C 381 (M⁺ + 1) N-e-82 NA N-b-81 nPr Me H1Me-5-1HIdz C 353 (M⁺ + 1) N-e-83 NB1 Int.n-56 BRA1 iPr Me Et 2-Nap C377 (M⁺ + 1) N-e-84 NA N-b-83 iPr Me H 2-Nap C 349 (M⁺ + 1) N-e-85 NB1Int.n-56 BRA2 iPr Me Et 5-Ind C 366 (M⁺ + 1) N-e-86 NA N-b-85 iPr Me H5-Ind C 338 (M⁺ + 1) N-e-87 NB1 Int.n-56 BRA3 iPr Me Et 1Me-5-Ind C 380(M⁺ + 1) N-e-88 NA N-b-87 iPr Me H 1Me-5-Ind C 352 (M⁺ + 1) N-e-89 NB1Int.n-56 BRA5 iPr Me Et 5-1HIdz C 367 (M⁺ + 1) N-e-90 NA N-b-89 iPr Me H5-1HIdz C 339 (M⁺ + 1) N-e-91 NB1 Int.n-56 BRA6 iPr Me Et 1Me-5-1HIdz C381 (M⁺ + 1) N-e-92 NA N-b-91 iPr Me H 1Me-5-1HIdz C 353 (M⁺ + 1) N-e-93NB1 Int.n-57 BRA1 nBu Me Et 2-Nap C 391 (M⁺ + 1) N-e-94 NA N-b-93 nBu MeH 2-Nap C 363 (M⁺ + 1) N-e-95 NB1 Int.n-57 BRA2 nBu Me Et 5-Ind C 380(M⁺ + 1) N-e-96 NA N-b-95 nBu Me H 5-Ind C 352 (M⁺ + 1)

TABLE N-E-5 LCMS Exp. Syn SM1 SM2 Rz Ry Y AR method RTime Mass N-e-97NB1 Int.n-57 BRA3 nBu Me Et 1Me-5-Ind C 394 (M⁺ + 1) N-e-98 NA N-e-97nBu Me H 1Me-5-Ind C 366 (M⁺ + 1) N-e-99 NB1 Int.n-57 BRA5 nBu Me Et5-1HIdz C 381 (M⁺ + 1) N-e-100 NA N-e-99 nBu Me H 5-1HIdz C 353 (M⁺ + 1)N-e-101 NB1 Int.n-57 BRA6 nBu Me Et 1Me-5-1HIdz C 395 (M⁺ + 1) N-e-102NA N-e-101 nBu Me H 1Me-5-1HIdz C 367 (M⁺ + 1) N-e-103 NB1 Int.n-58 BRA1iBu Me Et 2-Nap C 391 (M⁺ + 1) N-e-104 NA N-e-103 iBu Me H 2-Nap C 363(M⁺ + 1) N-e-105 NB1 Int.n-58 BRA2 iBu Me Et 5-Ind C 380 (M⁺ + 1)N-e-106 NA N-e-105 iBu Me H 5-Ind C 352 (M⁺ + 1) N-e-107 NB1 Int.n-58BRA3 iBu Me Et 1Me-5-Ind C 394 (M⁺ + 1) N-e-108 NA N-e-107 iBu Me H1Me-5-Ind C 366 (M⁺ + 1) N-e-109 NB1 Int.n-58 BRA5 iBu Me Et 5-1HIdz C381 (M⁺ + 1) N-e-110 NA N-e-109 iBu Me H 5-1HIdz C 353 (M⁺ + 1) N-e-111NB1 Int.n-58 BRA6 iBu Me Et 1Me-5-1HIdz C 395 (M⁺ + 1) N-e-112 NAN-e-111 iBu Me H 1Me-5-1HIdz C 367 (M⁺ + 1) N-e-113 NB1 Int.n-62 BRA1 BnH Et 2-Nap C 411 (M⁺ + 1) N-e-114 NA N-e-113 Bn H H 2-Nap C 383 (M⁺ + 1)N-e-115 NB1 Int.n-62 BRA2 Bn H Et 5-Ind C 400 (M⁺ + 1) N-e-116 NAN-e-115 Bn H H 5-Ind C 372 (M⁺ + 1) N-e-117 NB1 Int.n-62 BRA3 Bn H Et1Me-5-Ind C 414 (M⁺ + 1) N-e-118 NA N-e-117 Bn H H 1Me-5-Ind C 386(M⁺ + 1) N-e-119 NB1 Int.n-62 BRA5 Bn H Et 5-1HIdz C 401 (M⁺ + 1)N-e-120 NA N-e-119 Bn H H 5-1HIdz C 373 (M⁺ + 1) N-e-121 NB1 Int.n-62BRA6 Bn H Et 1Me-5-1HIdz C 415 (M⁺ + 1) N-e-122 NA N-e-121 Bn H H1Me-5-1HIdz C 387 (M⁺ + 1) N-e-123 NB1 Int.n-63 BRA1 4MeBn H Et 2-Nap C425 (M⁺ + 1) N-e-124 NA N-e-123 4MeBn H H 2-Nap C 397 (M⁺ + 1) N-e-125NB1 Int.n-63 BRA2 4MeBn Me Et 5-Ind C 414 (M⁺ + 1) N-e-126 NA N-e-1254MeBn Me H 5-Ind C 386 (M⁺ + 1) N-e-127 NB1 Int.n-63 BRA5 4MeBn Me Et5-1HIdz C 415 (M⁺ + 1) N-e-128 NA N-e-127 4MeBn Me H 5-1HIdz C 387(M⁺ + 1) N-e-129 NB1 Int.n-64 BRA2 3MeBn Me Et 5-Ind C 414 (M⁺ + 1)N-e-130 NA N-e-129 3MeBn Me H 5-Ind C 386 (M⁺ + 1) N-e-131 NB1 Int.n-64BRA3 3MeBn Me Et 1Me-5-Ind C 428 (M⁺ + 1) N-e-132 NA N-e-131 3MeBn Me H1Me-5-Ind C 400 (M⁺ + 1) N-e-133 NB1 Int.n-64 BRA5 3MeBn Me Et 5-1HIdz C415 (M⁺ + 1) N-e-134 NA N-e-133 3MeBn Me H 5-1HIdz C 387 (M⁺ + 1)N-e-135 NB1 Int.n-65 BRA1 2MeBn Me Et 2-Nap C 425 (M⁺ + 1) N-e-136 NAN-e-135 2MeBn Me H 2-Nap C 397 (M⁺ + 1) N-e-137 NB1 Int.n-65 BRA3 2MeBnMe Et 1Me-5-Ind C 428 (M⁺ + 1) N-e-138 NA N-e-137 2MeBn Me H 1Me-5-Ind C400 (M⁺ + 1) N-e-139 NB1 Int.n-65 BRA6 2MeBn Me Et 1Me-5-1HIdz C 429(M⁺ + 1) N-e-140 NA N-e-139 2MeBn Me H 1Me-5-1HIdz C 401 (M⁺ + 1)

TABLE N-E-6 LCMS Exp. Syn SM1 SM2 Rz Ry Y AR method RTime Mass N-e-141NB1 Int.n-66 BRA1 4FBn H Et 2-Nap C 429 (M⁺ + 1) N-e-142 NA N-e-141 4FBnH H 2-Nap C 401 (M⁺ + 1) N-e-143 NB1 Int.n-66 BRA3 4FBn H Et 1Me-5-Ind C432 (M⁺ + 1) N-e-144 NA N-e-143 4FBn H H 1Me-5-Ind C 404 (M⁺ + 1)N-e-145 NB1 Int.n-66 BRA6 4FBn H Et 1Me-5-1HIdz C 433 (M⁺ + 1) N-e-146NA N-e-145 4FBn H H 1Me-5-1HIdz C 405 (M⁺ + 1) N-e-147 NB1 Int.n-67 BRA13FBn H Et 2-Nap C 429 (M⁺ + 1) N-e-148 NA N-e-147 3FBn H H 2-Nap C 401(M⁺ + 1) N-e-149 NB1 Int.n-67 BRA2 3FBn H Et 5-Ind C 418 (M⁺ + 1)N-e-150 NA N-e-149 3FBn H H 5-Ind C 390 (M⁺ + 1) N-e-151 NB1 Int.n-67BRA3 3FBn H Et 1Me-5-Ind C 432 (M⁺ + 1) N-e-152 NA N-e-151 3FBn H H1Me-5-Ind C 404 (M⁺ + 1) N-e-153 NB1 Int.n-68 BRA3 2FBn H Et 1Me-5-Ind C432 (M⁺ + 1) N-e-154 NA N-e-153 2FBn H H 1Me-5-Ind C 404 (M⁺ + 1)N-e-155 NB1 Int.n-68 BRA5 2FBn H Et 5-1HIdz C 419 (M⁺ + 1) N-e-156 NAN-e-155 2FBn H H 5-1HIdz C 391 (M⁺ + 1) N-e-157 NB1 Int.n-68 BRA6 2FBn HEt 1Me-5-1HIdz C 433 (M⁺ + 1) N-e-158 NA N-e-157 2FBn H H 1Me-5-1HIdz C405 (M⁺ + 1) N-e-159 NB1 Int.n-69 BRA1 4MeOPh H Et 2-Nap C 427 (M⁺ + 1)N-e-160 NA N-e-159 4MeOPh H H 2-Nap C 399 (M⁺ + 1) N-e-161 NB1 Int.n-69BRA2 4MeOPh H Et 5-Ind C 416 (M⁺ + 1) N-e-162 NA N-e-161 4MeOPh H H5-Ind C 388 (M⁺ + 1) N-e-163 NB1 Int.n-69 BRA3 4MeOPh H Et 1Me-5-Ind C430 (M⁺ + 1) N-e-164 NA N-e-163 4MeOPh H H 1Me-5-Ind C 402 (M⁺ + 1)N-e-165 NB1 Int.n-69 BRA5 4MeOPh H Et 5-1HIdz C 417 (M⁺ + 1) N-e-166 NAN-e-165 4MeOPh H H 5-1HIdz C 389 (M⁺ + 1) N-e-167 NB1 Int.n-70 BRA13MeOPh H Et 2-Nap C 427 (M⁺ + 1) N-e-168 NA N-e-167 3MaOPh H H 2-Nap C399 (M⁺ + 1) N-e-169 NB1 Int.n-70 BRA3 3MeOPh H Et 1Me-5-Ind C 430(M⁺ + 1) N-e-170 NA N-e-169 3MeOPh H H 1Me-5-Ind C 402 (M⁺ + 1) N-e-171NB1 Int.n-70 BRA6 3MeOPh H Et 1Me-5-1HIdz C 431 (M⁺ + 1) N-e-172 NAN-e-171 3MeOPh H H 1Me-5-1HIdz C 403 (M⁺ + 1) N-e-173 NB1 Int.n-71 BRA52MeOPh H Et 5-1HIdz C 417 (M⁺ + 1) N-e-174 NA N-e-173 2MeOPh H H 5-1HIdzC 389 (M⁺ + 1) N-e-175 NB1 Int.n-71 BRA6 2MeOPh H Et 1Me-5-1HIdz C 431(M⁺ + 1) N-e-176 NA N-e-175 2MeOPh H H 1Me-5-1HIdz C 403 (M⁺ + 1)N-e-177 NB1 Int.n-71 BRA11 2MeOPh H Et 6-Qu C 428 (M⁺ + 1) N-e-178 NAN-e-177 2MeOPh H H 6-Qu C 400 (M⁺ + 1) N-e-179 NB1 Int.n-72 BRA1 4CF3PhH Et 2-Nap C 465 (M⁺ + 1) N-e-180 NA N-e-179 4CF3Ph H H 2-Nap C 437(M⁺ + 1) N-e-181 NB1 Int.n-72 BRA3 4CF3Ph H Et 1Me-5-Ind C 468 (M⁺ + 1)N-e-182 NA N-e-181 4CF3Ph H H 1Me-5-Ind C 440 (M⁺ + 1) N-e-183 NB1Int.n-72 BRA5 4CF3Ph H Et 5-1HIdz C 455 (M⁺ + 1) N-e-184 NA N-e-1834CF3Ph H H 5-1HIdz C 427 (M⁺ + 1) N-e-185 NB1 Int.n-72 BRA6 4CF3Ph H Et1Me-5-1HIdz C 469 (M⁺ + 1) N-e-186 NA N-e-185 4CF3Ph H H 1Me-5-1HIdz C441 (M⁺ + 1)

TABLE N-E-7 LCMS Exp. Syn SM1 SM2 Rz Ry Y AR method RTime Mass N-e-187NB1 Int.n-73 BRA1 2EtOPh H Et 2-Nap C 441 (M⁺ + 1) N-e-188 NA N-e-1872EtOPh H H 2-Nap C 413 (M⁺ + 1) N-e-189 NB1 Int.n-73 BRA3 2EtOPh H Et1Me-5-Ind C 444 (M⁺ + 1) N-e-190 NA N-e-189 2EtOPh H H 1Me-5-Ind C 416(M⁺ + 1) N-e-191 NB1 Int.n-73 BRA6 2EtOPh H Et 1Me-5-1HIdz C 445(M⁺ + 1) N-e-192 NA N-e-191 2EtOPh H H 1Me-5-1HIdz C 417 (M⁺ + 1)N-e-193 NB1 Int.n-74 BRA1 3iPrOPh H Et 2-Nap C 455 (M⁺ + 1) N-e-194 NAN-e-193 3iPrOPh H H 2-Nap C 427 (M⁺ + 1) N-e-195 NB1 Int.n-74 BRA23iPrOPh H Et 5-Ind C 444 (M⁺ + 1) N-e-196 NA N-e-195 3iPrOPh H H 5-Ind C416 (M⁺ + 1) N-e-197 NB1 Int.n-74 BRA3 3iPrOPh H Et 1Me-5-Ind C 458(M⁺ + 1) N-e-198 NA N-b-197 3iPrOPh H H 1Me-5-Ind C 430 (M⁺ + 1) N-e-199NB1 Int.n-75 BRA3 3,5DFPh H Et 1Me-5-Ind C 436 (M⁺ + 1) N-e-200 NAN-b-199 3,5DFPh H H 1Me-5-Ind C 408 (M⁺ + 1) N-e-201 NB1 Int.n-75 BRA53,5DFPh H Et 5-1HIdz C 423 (M⁺ + 1) N-e-202 NA N-b-201 3,5DFPh H H5-1HIdz C 395 (M⁺ + 1) N-e-203 NB1 Int.n-75 BRA6 3,5DFPh H Et1Me-5-1HIdz C 437 (M⁺ + 1) N-e-204 NA N-b-203 3,5DFPh H H 1Me-5-1HIdz C409 (M⁺ + 1)

Example N-f-1 Synthesis of methyl3-[3-(naphthalen-2-yl)-4-(N-phenylamino)phenyl]propionate (Compound No.N-f-1) (Synthesis method NB2)

A solution of Intermediate n-7 (306.1 mg) in dehydrated toluene (1 ml)was added with aniline (1 ml, TCI), palladium acetate (20.2 mg, WAKO),2-(di-t-butylphosphine)biphenyl (39 mg, Across) and cesium carbonate(863.4 mg, WAKO), and stirred at 90° C. for 18 hours. The reactionmixture was added with ethyl acetate (40 ml), and washed successivelywith saturated aqueous sodium hydrogencarbonate, saturated aqueousammonium chloride and saturated brine. The organic layer was dried, andthen the solvent was evaporated under reduced pressure. The residue waspurified by column chromatography (Quad, hexane:ethyl acetate=4:1) toobtain the title compound (Compound No. N-f-1, 101.4 mg).

Examples N-f-1 to N-f-92

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-N-F-1 and Table-N-F-2. Inthe tables, the compound numbers are mentioned in the columns indicatedas “Exp.”. In the tables, corresponding methods among the aforementionedsynthesis methods are shown in the columns of “Syn” with symbols, thestarting compounds 1 are mentioned in the columns of “SM1”, and thestarting compounds 2 are mentioned in the columns of “SM2”.

TABLE-N-F-1

LCMS Exp. Syn SM1 SM2 Rz Ry Y AR method RTime Mass N-f-1 NB2 Int.n-7BRA14 Ph H Me 2-Nap C 383 (M⁺ + 1) N-f-2 NA N-f-1 Ph H H 2-Nap C 369(M⁺ + 1) N-f-3 NB2 Int.n-8 BRA14 Ph H Me 5-Ind C 372 (M⁺ + 1) N-f-4 NAN-f-3 Ph H H 5-Ind C 358 (M⁺ + 1) N-f-5 NB2 Int.n-9 BRA14 Ph H Me1Me-5-Ind C 386 (M⁺ + 1) N-f-6 NA N-f-5 Ph H H 1Me-5-Ind C 372 (M⁺ + 1)N-f-7 NB2 Int.n-10 BRA14 Ph H Me 5-1HIdz C 373 (M⁺ + 1) N-f-8 NA N-f-7Ph H H 5-1HIdz C 359 (M⁺ + 1) N-f-9 NB2 Int.n-11 BRA14 Ph H Me1Me-5-1HIdz C 387 (M⁺ + 1) N-f-10 NA N-f-9 Ph H H 1Me-5-1HIdz C 373(M⁺ + 1) N-f-11 NB2 N-f-1 CHO1 Ph Me Me 2-Nap C 397 (M⁺ + 1) N-f-12 NAN-f-11 Ph Me H 2-Nap C 383 (M⁺ + 1) N-f-13 NB2 N-f-3 CHO1 Ph Me Me1Me-5-Ind C 400 (M⁺ + 1) N-f-14 NA N-f-13 Ph Me H 1ME-5-Ind C 386(M⁺ + 1) N-f-15 NB2 N-f-5 CHO1 Ph Me Me 1Me-5-1HIdz C 401 (M⁺ + 1)N-f-16 NA N-f-15 Ph Me H 1Me-5-1HIdz C 387 (M⁺ + 1) N-f-17 NB2 Int.n-7BRA29 4MePh H Me 2-Nap C 397 (M⁺ + 1) N-f-18 NA N-f-17 4MePh H H 2-Nap C383 (M⁺ + 1) N-f-19 NB2 Int.n-9 BRA29 4MePh H Me 1Me-5-Ind C 400(M⁺ + 1) N-f-20 NA N-f-19 4MePh H H 1Me-5-Ind C 386 (M⁺ + 1) N-f-21 NB2Int.n-11 BRA29 4MePh H Me 1Me-5-1HIdz C 401 (M⁺ + 1) N-f-22 NA N-f-214MePh H H 1Me-5-1HIdz C 387 (M⁺ + 1) N-f-23 NB2 Int.n-7 BRA60 3MePh H Me2-Nap C 397 (M⁺ + 1) N-f-24 NA N-f-23 3MePh H H 2-Nap C 383 (M⁺ + 1)N-f-25 NB2 Int.n-9 BRA60 3MePh H Me 1Me-5-Ind C 400 (M⁺ + 1) N-f-26 NAN-f-25 3MePh H H 1Me-5-Ind C 386 (M⁺ + 1) N-f-27 NB2 Int.n-11 BRA603MePh H Me 1Me-5-1HIdz C 401 (M⁺ + 1) N-f-28 NA N-f-27 3MePh H H1Me-5-1HIdz C 387 (M⁺ + 1) N-f-29 NB2 Int.n-7 BRA59 2MePh H Me 2-Nap C397 (M⁺ + 1) N-f-30 NA N-f-29 2MePh H H 2-Nap C 383 (M⁺ + 1) N-f-31 NB2Int.n-8 BRA59 2MePh H Me 5-Ind C 386 (M⁺ + 1) N-f-32 NA N-f-31 2MePh H H5-Ind C 372 (M⁺ + 1) N-f-33 NB2 Int.n-10 BRA59 2MePh H Me 5-1HIdz C 387(M⁺ + 1) N-f-34 NA N-f-33 2MePh H H 5-1HIdz C 373 (M⁺ + 1) N-f-35 NB2Int.n-7 BRA22 4FPh H Me 2-Nap C 401 (M⁺ + 1) N-f-36 NA N-f-35 4FPh H H2-Nap C 387 (M⁺ + 1) N-f-37 NB2 Int.n-8 BRA22 4FPh H Me 5-Ind C 390(M⁺ + 1) N-f-38 NA N-f-37 4FPh H H 5-Ind C 376 (M⁺ + 1) N-f-39 NB2Int.n-9 BRA22 4FPh H Me 1Me-5-Ind C 404 (M⁺ + 1) N-f-40 NA N-f-39 4FPh HH 1Me-5-Ind C 390 (M⁺ + 1) N-f-41 NB2 Int.n-7 BRA33 3FPh H Me 2-Nap C401 (M⁺ + 1) N-f-42 NA N-f-41 3FPh H H 2-Nap C 387 (M⁺ + 1) N-f-43 NB2Int.n-10 BRA33 3FPh H Me 5-1HIdz C 391 (M⁺ + 1) N-f-44 NA N-f-43 3FPh HH 5-1HIdz C 377 (M⁺ + 1) N-f-45 NB2 Int.n-11 BRA33 3FPh H Me 1Me-5-1HIdzC 405 (M⁺ + 1) N-f-46 NA N-f-45 3FPh H H 1Me-5-1HIdz C 391 (M⁺ + 1)

TABLE N-F-2 LCMS Exp. Syn SM1 SM2 Rz Ry Y AR method RTime Mass N-f-47NB2 Int.n-7 BRA32 2FPh H Me 2-Nap C 401 (M⁺ + 1) N-f-48 NA N-f-47 2FPh HH 2-Nap C 387 (M⁺ + 1) N-f-49 NB2 Int.n-8 BRA32 2FPh H Me 5-Ind C 390(M⁺ + 1) N-f-50 NA N-f-49 2FPh H H 5-Ind C 376 (M⁺ + 1) N-f-51 NB2Int.n-11 BRA32 2FPh H Me 1Me-5-1HIdz C 405 (M⁺ + 1) N-f-52 NA N-f-512FPh H H 1Me-5-1HIdz C 391 (M⁺ + 1) N-f-53 NB2 Int.n-8 BRA19 4MeOPh H Me5-Ind C 402 (M⁺ + 1) N-f-54 NA N-f-53 4MeOPh H H 5-Ind C 388 (M⁺ + 1)N-f-55 NB2 Int.n-10 BRA19 4MeOPh H Me 5-1HIdz C 403 (M⁺ + 1) N-f-56 NAN-f-55 4MeOPh H H 5-1HIdz C 389 (M⁺ + 1) N-f-57 NB2 Int.n-11 BRA194MeOPh Me Me 1Me-5-1HIdz C 417 (M⁺ + 1) N-f-58 NA N-f-57 4MeOPh Me H1Me-5-1HIdz C 403 (M⁺ + 1) N-f-59 NB2 Int.n-9 BRA37 3MeOPh Me Me1Me-5-Ind C 416 (M⁺ + 1) N-f-60 NA N-f-59 3MeOPh Me H 1Me-5-Ind C 402(M⁺ + 1) N-f-61 NB2 Int.n-10 BRA37 3MeOPh Me Me 5-1HIdz C 403 (M⁺ + 1)N-f-62 NA N-f-61 3MeOPh Me H 5-1HIdz C 389 (M⁺ + 1) N-f-63 NB2 Int.n-11BRA37 3MeOPh H Me 1Me-5-1HIdz C 417 (M⁺ + 1) N-f-64 NA N-f-63 3MeOPh H H1Me-5-1HIdz C 403 (M⁺ + 1) N-f-65 NB2 Int.n-7 BRA38 2MeOPh H Me 2-Nap C413 (M⁺ + 1) N-f-66 NA N-f-65 2MeOPh H H 2-Nap C 399 (M⁺ + 1) N-f-67 NB2Int.n-8 BRA38 2MeOPh H Me 5-Ind C 402 (M⁺ + 1) N-f-68 NA N-f-67 2MeOPh HH 5-Ind C 388 (M⁺ + 1) N-f-69 NB2 Int.n-11 BRA38 2MeOPh H Me 1Me-5-1HIdzC 417 (M⁺ + 1) N-f-70 NA N-f-69 2MeOPh H H 1Me-5-1HIdz C 403 (M⁺ + 1)N-f-71 NB2 Int.n-7 BRA41 4CF3Ph H Me 2-Nap C 451 (M⁺ + 1) N-f-72 NAN-f-71 4CF3Ph H H 2-Nap C 437 (M⁺ + 1) N-f-73 NB2 Int.n-9 BRA41 4CF3Ph HMe 1Me-5-Ind C 454 (M⁺ + 1) N-f-74 NA N-f-73 4CF3Ph H H 1Me-5-Ind C 440(M⁺ + 1) N-f-75 NB2 Int.n-11 BRA41 4CF3Ph H Me 1Me-5-1HIdz C 455(M⁺ + 1) N-f-76 NA N-f-75 4CF3Ph H H 1Me-5-1HIdz C 441 (M⁺ + 1) N-f-77NB2 Int.n-8 BRA88 4PhOPh H Me 5-Ind C 464 (M⁺ + 1) N-f-78 NA N-f-774PhOPh H H 5-Ind C 450 (M⁺ + 1) N-f-79 NB2 Int.n-9 BRA88 4PhOPh H Me1Me-5-Ind C 478 (M⁺ + 1) N-f-80 NA N-f-79 4PhOPh H H 1Me-5-Ind C 464(M⁺ + 1) N-f-81 NB2 Int.n-10 BRA88 4PhOPh H Me 5-1HIdz C 465 (M⁺ + 1)N-f-82 NA N-f-81 4PhOPh H H 5-1HIdz C 451 (M⁺ + 1) N-f-83 NB2 Int.n-7BRA61 2ClPh H Me 2-Nap C 417 (M⁺ + 1) N-f-84 NA N-f-83 2ClPh H H 2-Nap C403 (M⁺ + 1) N-f-85 NB2 Int.n-9 BRA61 2ClPh H Me 1Me-5-Ind C 420(M⁺ + 1) N-f-86 NA N-f-85 2ClPh H H 1Me-5-Ind C 406 (M⁺ + 1) N-f-87 NB2Int.n-10 BRA61 2ClPh H Me 5-1HIdz C 407 (M⁺ + 1) N-f-88 NA N-f-87 2ClPhH H 5-1HIdz C 393 (M⁺ + 1) N-f-89 NB2 Int.n-7 BRA73 3,5DMePh H Me 2-NapC 411 (M⁺ + 1) N-f-90 NA N-f-89 3,5DMePh H H 2-Nap C 397 (M⁺ + 1) N-f-91NB2 Int.n-9 BRA73 3,5DMePh H Me 1Me-5-Ind C 414 (M⁺ + 1) N-f-92 NAN-f-91 3,5DMePh H H 1Me-5-Ind C 400 (M⁺ + 1)

Example N-g-33 Synthesis of methyl3-[4-cyclopentylamino-3-methyl-5-(naphthalen-2-yl)phenyl]propionate(Compound No. N-e-33) (Synthesis method NB1)

According to the procedure described in the synthesis method of thecompound of Example N-a-1 (Synthesis method NB) provided that thereaction was carried out for 18 hours, and the column chromatography wasperformed with hexane:ethyl acetate=4:1), the compound of Example N-g-1(91.6 mg), methyl boronate (140.0 mg, Ald), 2 M aqueous sodium carbonate(300 μl) and (Ph₃P)₄Pd (75.5 mg) were reacted and treated to obtain thetitle compound (Compound No. N-g-33, 41.3 mg).

Example N-g-251 Synthesis of methyl3-[4-(N-methyl-N-cyclopentylamino)-3-(N-methylamino)-5-(naphthalen-2-yl)phenyl]propionate(Compound No. N-g-251) (Synthesis method NN1)

A solution of Compound No. N-g-131 (102 mg) in DMF (3 ml) was added with60% sodium hydride (7 mg) under ice cooling, and stirred for 10 minutes.This reaction mixture was added with methyl iodide (17 μl), stirred for10 minutes, then warmed to room temperature, and further stirred for 2hours. The reaction mixture was poured into water, and added with ethylacetate (30 ml) for extraction. The organic layer was washedsuccessively with saturated aqueous sodium hydrogencarbonate, saturatedaqueous ammonium chloride and saturated brine, and dried, and then thesolvent was evaporated under reduced pressure. The residue was purifiedby column chromatography (Quad, hexane:ethyl acetate=3:1) to obtain thetitle compound (Compound No. N-g-251, 30 mg).

Example N-g-285 Synthesis of methyl3-[3-(N-dimethylamino)-4-(N-methyl-N-cyclopentylamino)-5-(naphthalen-2-yl)phenyl]propionate(Compound No. N-g-285) (Synthesis method NN2)

A solution of Compound No. N-g-131 (102 mg) in DMF (3 ml) was added with60% sodium hydride (20 mg) under ice cooling, and stirred for 10minutes. This reaction mixture was added dropwise with methyl iodide(100 μl), stirred for 10 minutes, then warmed to room temperature, andfurther stirred for 16 hours. The reaction mixture was poured intowater, and added with ethyl acetate (30 ml) for extraction. The organiclayer was washed successively with saturated aqueous sodiumhydrogencarbonate, saturated aqueous ammonium chloride and saturatedbrine, and dried, and then the solvent was evaporated under reducedpressure. The residue was purified by column chromatography (Quad,hexane:ethyl acetate 3:1) to obtain the title compound (Compound No.N-g-285, 80 mg).

Examples N-g-1 to N-g-318

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification including theexamples described above are shown in Table-N-G-1 to Table-N-G-7. In thetables, the compound numbers are mentioned in the columns indicated as“Exp.”. In the tables, used methods among the aforementioned synthesismethods are shown in the columns of “Syn” with symbols, the startingcompounds 1 are mentioned in the columns of “SM1”, and the startingcompounds 2 are mentioned in the columns of “SM2”.

TABLE-N-G-1

LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-g-1 NB1 Int.n-39BRA1 cPen H Me Br 2-Nap C 452 (M⁺) N-g-2 NA N-g-1 cPen H H Br 2-Nap C438 (M⁺) N-g-3 NB1 Int.n-39 BRA2 cPen H Me Br 5-Ind C 441 (M⁺) N-g-4 NAN-g-3 cPen H H Br 5-Ind C 427 (M⁺) N-g-5 NB1 Int.n-39 BRA3 cPen H Me Br1Me-5-Ind C 455 (M⁺) N-g-6 NA N-g-5 cPen H H Br 1Me-5-Ind C 441 (M⁺)N-g-7 NB1 Int.n-39 BRA5 cPen H Me Br 5-1HIdz C 442 (M⁺) N-g-8 NA N-g-7cPen H H Br 5-1HIdz C 428 (M⁺) N-g-9 NB1 Int.n-39 BRA6 cPen H Me Br1Me-5-1HIdz C 456 (M⁺) N-g-10 NA N-g-9 cPen H H Br 1Me-5-1HIdz C 442(M⁺) N-g-11 NB1 Int.n-39 BRA11 cPen H Me Br 6-Qu C 453 (M⁺) N-g-12 NAN-g-11 cPen H H Br 6-Qu C 439 (M⁺) N-g-13 NC2 N-g-1 CHO1 cPen Me Me Br2-Nap C 466 (M⁺) N-g-14 NA N-g-13 cPen Me H Br 2-Nap C 452 (M⁺) N-g-15NC2 N-g-5 CHO1 cPen Me Me Br 1Me-5-Ind C 455 (M⁺) N-g-16 NA N-g-15 cPenMe H Br 1Me-5-Ind C 441 (M⁺) N-g-17 NB1 Int.n-41 BRA2 nPr H Me Br 5-IndC 415 (M⁺) N-g-18 NA N-g-17 nPr H H Br 5-Ind C 401 (M⁺) N-g-19 NB1Int.n-41 BRA3 nPr H Me Br 1Me-5-Ind C 429 (M⁺) N-g-20 NA N-g-19 nPr H HBr 1Me-5-Ind C 415 (M⁺) N-g-21 NB1 Int.n-41 BRA5 nPr H Me Br 5-1HIdz C416 (M⁺) N-g-22 NA N-g-21 nPr H H Br 5-1HIdz C 402 (M⁺) N-g-23 NB1Int.n-41 BRA11 nPr H Me Br 6-Qu C 427 (M⁺) N-g-24 NA N-g-23 nPr H H Br6-Qu C 413 (M⁺) N-g-25 NB1 Int.n-43 BRA1 iPr H Me Br 2-Nap C 426 (M⁺)N-g-26 NA N-g-25 iPr H H Br 2-Nap C 412 (M⁺) N-g-27 NB1 Int.n-43 BRA2iPr H Me Br 5-Ind C 415 (M⁺) N-g-28 NA N-g-27 iPr H H Br 5-Ind C 401(M⁺) N-g-29 NB1 Int.n-43 BRA6 iPr H Me Br 1Me-5-1HIdz C 430 (M⁺) N-g-30NA N-g-29 iPr H H Br 1Me-5-1HIdz C 416 (M⁺) N-g-31 NB1 Int.n-43 BRA10iPr H Me Br 3-Qu C 427 (M⁺) N-g-32 NA N-g-31 iPr H H Br 3-Qu C 413 (M⁺)N-g-33 NB1 N-g-1 BRA13 cPen H Me Me 2-Nap C 388 (M⁺ + 1) N-g-34 NAN-g-33 cPen H H Me 2-Nap C 374 (M⁺ + 1) N-g-35 NB1 N-g-3 BRA13 cPen H MeMe 5-Ind C 377 (M⁺ + 1) N-g-36 NA N-g-35 cPen H H Me 5-Ind C 363(M⁺ + 1) N-g-37 NB1 N-g-5 BRA13 cPen H Me Me 1Me-5-Ind C 391 (M⁺ + 1)N-g-38 NA N-g-37 cPen H H Me 1Me-5-Ind C 377 (M⁺ + 1) N-g-39 NB1 N-g-7BRA13 cPen H Me Me 5-1HIdz C 378 (M⁺ + 1) N-g-40 NA N-g-39 cPen H H Me5-1HIdz C 364 (M⁺ + 1) N-g-41 NB1 N-g-9 BRA13 cPen H Me Me 1Me-5-1HIdz C392 (M⁺ + 1) N-g-42 NA N-g-41 cPen H H Me 1Me-5-1HIdz C 378 (M⁺ + 1)N-g-43 NC2 N-g-37 CHO1 cPen Me Me Me 1Me-5-Ind C 405 (M⁺ + 1) N-g-44 NAN-g-43 cPen Me H Me 1Me-5-Ind C 391 (M⁺ + 1)

TABLE N-G-2 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-g-45NB1 Int.n-77 BRA1 cPen H Me NO2 2-Nap C 419 (M⁺ + 1) N-g-46 NA N-g-45cPen H H NO2 2-Nap C 405 (M⁺ + 1) N-g-47 NB1 Int.n-77 BRA2 cPen H Me NO25-Ind C 408 (M⁺ + 1) N-g-48 NA N-g-47 cPen H H NO2 5-Ind C 394 (M⁺ + 1)N-g-49 NB1 Int.n-77 BRA3 cPen H Me NO2 1Me-5-Ind C 422 (M⁺ + 1) N-g-50NA N-g-49 cPen H H NO2 1Me-5-Ind C 408 (M⁺ + 1) N-g-51 NB1 Int.n-77 BRA5cPen H Me NO2 5-1HIdz C 409 (M⁺ + 1) N-g-52 NA N-g-51 cPen H H NO25-1HIdz C 395 (M⁺ + 1) N-g-53 NB1 Int.n-77 BRA6 cPen H Me NO21Me-5-1HIdz C 423 (M⁺ + 1) N-g-54 NA N-g-53 cPen H H NO2 1Me-5-1HIdz C409 (M⁺ + 1) N-g-55 NB1 Int.n-78 BRA1 nPr H Me NO2 2-Nap C 393 (M⁺ + 1)N-g-56 NA N-g-55 nPr H H NO2 2-Nap C 379 (M⁺ + 1) N-g-57 NB1 Int.n-78BRA2 nPr H Me NO2 5-Ind C 382 (M⁺ + 1) N-g-58 NA N-g-57 nPr H H NO25-Ind C 368 (M⁺ + 1) N-g-59 NB1 Int.n-78 BRA3 nPr H Me NO2 1Me-5-Ind C396 (M⁺ + 1) N-g-60 NA N-g-59 nPr H H NO2 1Me-5-Ind C 382 (M⁺ + 1)N-g-61 NB1 Int.n-78 BRA5 nPr H Me NO2 5-1HIdz C 383 (M⁺ + 1) N-g-62 NAN-g-61 nPr H H NO2 5-1HIdz C 369 (M⁺ + 1) N-g-63 NB1 Int.n-78 BRA6 nPr HMe NO2 1Me-5-1HIdz C 397 (M⁺ + 1) N-g-64 NA N-g-63 nPr H H NO21Me-5-1HIdz C 383 (M⁺ + 1) N-g-65 NB1 Int.n-79 BRA1 iPr H Me NO2 2-Nap C393 (M⁺ + 1) N-g-66 NA N-g-65 iPr H H NO2 2-Nap C 379 (M⁺ + 1) N-g-67NB1 Int.n-79 BRA2 iPr H Me NO2 5-Ind C 382 (M⁺ + 1) N-g-68 NA N-g-67 iPrH H NO2 5-Ind C 368 (M⁺ + 1) N-g-69 NB1 Int.n-79 BRA3 iPr H Me NO21Me-5-Ind C 396 (M⁺ + 1) N-g-70 NA N-g-69 iPr H H NO2 1Me-5-Ind C 382(M⁺ + 1) N-g-71 NB1 Int.n-79 BRA5 iPr H Me NO2 5-1HIdz C 383 (M⁺ + 1)N-g-72 NA N-g-71 iPr H H NO2 5-1HIdz C 369 (M⁺ + 1) N-g-73 NB1 Int.n-79BRA6 iPr H Me NO2 1Me-5-1HIdz C 397 (M⁺ + 1) N-g-74 NA N-g-73 iPr H HNO2 1Me-5-1HIdz C 383 (M⁺ + 1) N-g-75 NB1 Int.n-83 BRA1 cPen Me Me NO22-Nap C 433 (M⁺ + 1) N-g-76 NA N-g-75 cPen Me H NO2 2-Nap C 419 (M⁺ + 1)N-g-77 NB1 Int.n-83 BRA3 cPen Me Me NO2 1Me-5-Ind C 436 (M⁺ + 1) N-g-78NA N-g-77 cPen Me H NO2 1Me-5-Ind C 422 (M⁺ + 1) N-g-79 NB1 Int.n-83BRA6 cPen Me Me NO2 1Me-5-1HIdz C 437 (M⁺ + 1) N-g-80 NA N-g-79 cPen MeH NO2 1Me-5-1HIdz C 423 (M⁺ + 1) N-g-81 NB1 Int.n-84 BRA1 nPr Me Me NO22-Nap C 407 (M⁺ + 1) N-g-82 NA N-g-81 nPr Me H NO2 2-Nap C 393 (M⁺ + 1)N-g-83 NB1 Int.n-84 BRA2 nPr Me Me NO2 5-Ind C 396 (M⁺ + 1) N-g-84 NAN-g-83 nPr Me H NO2 5-Ind C 382 (M⁺ + 1) N-g-85 NB1 Int.n-84 BRA3 nPr MeMe NO2 1Me-5-Ind C 410 (M⁺ + 1) N-g-86 NA N-g-85 nPr Me H NO2 1Me-5-IndC 396 (M⁺ + 1) N-g-87 NB1 Int.n-84 BRA5 nPr Me Me NO2 5-1HIdz C 397(M⁺ + 1) N-g-88 NA N-g-87 nPr Me H NO2 5-1HIdz C 383 (M⁺ + 1) N-g-89 NB1Int.n-84 BRA6 nPr Me Me NO2 1Me-5-1HIdz C 411 (M⁺ + 1) N-g-90 NA N-g-89nPr Me H NO2 1Me-5-1HIdz C 397 (M⁺ + 1) N-g-91 NB1 Int.n-85 BRA1 iPr MeMe NO2 2-Nap C 407 (M⁺ + 1) N-g-92 NA N-g-91 iPr Me H NO2 2-Nap C 393(M⁺ + 1)

TABLE N-G-3 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-g-93NB1 Int.n-85 BRA2 iPr Me Me NO2 5-Ind C 396 (M⁺ + 1) N-g-94 NA N-g-93iPr Me H NO2 5-Ind C 382 (M⁺ + 1) N-g-95 NB1 Int.n-85 BRA3 iPr Me Me NO21Me-5-Ind C 410 (M⁺ + 1) N-g-96 NA N-g-95 iPr Me H NO2 1Me-5-Ind C 396(M⁺ + 1) N-g-97 NB1 Int.n-85 BRA5 iPr Me Me NO2 5-1HIdz C 397 (M⁺ + 1)N-g-98 NA N-g-97 iPr Me H NO2 5-1HIdz C 383 (M⁺ + 1) N-g-99 NB1 Int.n-85BRA6 iPr Me Me NO2 1Me-5-1HIdz C 411 (M⁺ + 1) N-g-100 NA N-g-99 iPr Me HNO2 1Me-5-1HIdz C 397 (M⁺ + 1) N-g-101 ND1 N-g-45 cPen H Me NH2 2-Nap C389 (M⁺ + 1) N-g-102 NA N-g-101 cPen H H NH2 2-Nap C 375 (M⁺ + 1)N-g-103 ND1 N-g-47 cPen H Me NH2 5-Ind C 378 (M⁺ + 1) N-g-104 NA N-g-103cPen H H NH2 5-Ind C 364 (M⁺ + 1) N-g-105 ND1 N-g-49 cPen H Me NH21Me-5-Ind C 392 (M⁺ + 1) N-g-106 NA N-g-105 cPen H H NH2 1Me-5-Ind C 378(M⁺ + 1) N-g-107 ND1 N-g-51 cPen H Me NH2 5-1HIdz C 379 (M⁺ + 1) N-g-108NA N-g-107 cPen H H NH2 5-1HIdz C 365 (M⁺ + 1) N-g-109 ND1 N-g-53 cPen HMe NH2 1Me-5-1HIdz C 393 (M⁺ + 1) N-g-110 NA N-g-109 cPen H H NH21Me-5-1HIdz C 379 (M⁺ + 1) N-g-111 ND1 N-g-55 nPr H Me NH2 2-Nap C 363(M⁺ + 1) N-g-112 NA N-g-111 nPr H H NH2 2-Nap C 349 (M⁺ + 1) N-g-113 ND1N-g-57 nPr H Me NH2 5-Ind C 352 (M⁺ + 1) N-g-114 NA N-g-113 nPr H H NH25-Ind C 338 (M⁺ + 1) N-g-115 ND1 N-g-59 nPr H Me NH2 1Me-5-Ind C 366(M⁺ + 1) N-g-116 NA N-g-115 nPr H H NH2 1Me-5-Ind C 352 (M⁺ + 1) N-g-117ND1 N-g-61 nPr H Me NH2 5-1HIdz C 353 (M⁺ + 1) N-g-118 NA N-g-117 nPr HH NH2 5-1HIdz C 339 (M⁺ + 1) N-g-119 ND1 N-g-63 nPr H Me NH2 1Me-5-1HIdzC 367 (M⁺ + 1) N-g-120 NA N-g-119 nPr H H NH2 1Me-5-1HIdz C 353 (M⁺ + 1)N-g-121 ND1 N-g-65 iPr H Me NH2 2-Nap C 363 (M⁺ + 1) N-g-122 NA N-g-121iPr H H NH2 2-Nap C 349 (M⁺ + 1) N-g-123 ND1 N-g-67 iPr H Me NH2 5-Ind C352 (M⁺ + 1) N-g-124 NA N-g-123 iPr H H NH2 5-Ind C 338 (M⁺ + 1) N-g-125ND1 N-g-69 iPr H Me NH2 1Me-5-Ind C 336 (M⁺ + 1) N-g-126 NA N-g-125 iPrH H NH2 1Me-5-Ind C 352 (M⁺ + 1) N-g-127 ND1 N-g-71 iPr H Me NH2 5-1HIdzC 353 (M⁺ + 1) N-g-128 NA N-g-127 iPr H H NH2 5-1HIdz C 339 (M⁺ + 1)N-g-129 ND1 N-g-73 iPr H Me NH2 1Me-5-1HIdz C 367 (M⁺ + 1) N-g-130 NAN-g-129 iPr H H NH2 1Me-5-1HIdz C 353 (M⁺ + 1) N-g-131 NC1 N-g-75 cPenMe Me NH2 2-Nap C 389 (M⁺ + 1) N-g-132 NA N-g-131 cPen Me H NH2 2-Nap C375 (M⁺ + 1) N-g-133 NC1 N-g-77 cPen Me Me NH2 1Me-5-Ind C 392 (M⁺ + 1)N-g-134 NA N-g-133 cPen Me H NH2 1Me-5-Ind C 378 (M⁺ + 1) N-g-135 NC1N-g-79 cPen Me Me NH2 5-1HIdz C 379 (M⁺ + 1) N-g-136 NA N-g-135 cPen MeH NH2 5-1HIdz C 365 (M⁺ + 1) N-g-137 NC1 N-g-81 cPen Me Me NH21Me-5-1HIdz C 393 (M⁺ + 1) N-g-138 NA N-g-137 cPen Me H NH2 1Me-5-1HIdzC 379 (M⁺ + 1)

TABLE N-G-4 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-g-139 ND1 N-g-83 nPr Me Me NH2 2-Nap C 363 (M⁺ + 1) N-g-140 NA N-g-139nPr Me H NH2 2-Nap C 349 (M⁺ + 1) N-g-141 ND1 N-g-85 nPr Me Me NH2 5-IndC 352 (M⁺ + 1) N-g-142 NA N-g-141 nPr Me H NH2 5-Ind C 338 (M⁺ + 1)N-g-143 ND1 N-g-87 nPr Me Me NH2 1Me-5-Ind C 366 (M⁺ + 1) N-g-144 NAN-g-143 nPr Me H NH2 1Me-5-Ind C 352 (M⁺ + 1) N-g-145 ND1 N-g-89 nPr MeMe NH2 5-1HIdz C 353 (M⁺ + 1) N-g-146 NA N-g-145 nPr Me H NH2 5-1HIdz C339 (M⁺ + 1) N-g-147 ND1 N-g-91 nPr Me Me NH2 1Me-5-1HIdz C 367 (M⁺ + 1)N-g-148 NA N-g-147 nPr Me H NH2 1Me-5-1HIdz C 353 (M⁺ + 1) N-g-149 ND1N-g-93 iPr Me Me NH2 2-Nap C 363 (M⁺ + 1) N-g-150 NA N-g-149 iPr Me HNH2 2-Nap C 349 (M⁺ + 1) N-g-151 ND1 N-g-95 iPr Me Me NH2 1Me-5-Ind C366 (M⁺ + 1) N-g-152 NA N-g-151 iPr Me H NH2 1Me-5-Ind C 352 (M⁺ + 1)N-g-153 ND1 N-g-97 iPr Me Me NH2 5-1HIdz C 353 (M⁺ + 1) N-g-154 NAN-g-153 iPr Me H NH2 5-1HIdz C 339 (M⁺ + 1) N-g-155 ND1 N-g-99 iPr Me MeNH2 1Me-5-1HIdz C 367 (M⁺ + 1) N-g-156 NA N-g-155 iPr Me H NH21Me-5-1HIdz C 353 (M⁺ + 1) N-g-157 NB1 Int.n-80 BRA1 2-Indane H Me NO22-Nap C 467 (M⁺ + 1) N-g-158 NA N-g-157 2-Indane H H NO2 2-Nap C 453(M⁺ + 1) N-g-159 NB1 Int.n-80 BRA2 2-Indane H Me NO2 5-Ind C 456(M⁺ + 1) N-g-160 NA N-g-159 2-Indane H H NO2 5-Ind C 442 (M⁺ + 1)N-g-161 NB1 Int.n-80 BRA3 2-Indane H Me NO2 1Me-5-Ind C 470 (M⁺ + 1)N-g-162 NA N-g-161 2-Indane H H NO2 1Me-5-Ind C 456 (M⁺ + 1) N-g-163 NB1Int.n-80 BRA5 2-Indane H Me NO2 5-1HIdz C 457 (M⁺ + 1) N-g-164 NAN-g-163 2-Indane H H NO2 5-1HIdz C 443 (M⁺ + 1) N-g-165 NB1 Int.n-80BRA6 2-Indane H Me NO2 1Me-5-1HIdz C 471 (M⁺ + 1) N-g-166 NA N-g-1652-Indane H H NO2 1Me-5-1HIdz C 457 (M⁺ + 1) N-g-167 NB1 Int.n-81 BRA2cHex H Me NO2 5-Ind C 422 (M⁺ + 1) N-g-168 NA N-g-167 cHex H H NO2 5-IndC 408 (M⁺ + 1) N-g-169 NB1 Int.n-81 BRA3 cHex H Me NO2 1Me-5-Ind C 436(M⁺ + 1) N-g-170 NA N-g-169 cHex H H NO2 1Me-5-Ind C 422 (M⁺ + 1)N-g-171 NB1 Int.n-81 BRA5 cHex H Me NO2 5-1HIdz C 423 (M⁺ + 1) N-g-172NA N-g-171 cHex H H NO2 5-1HIdz C 409 (M⁺ + 1) N-g-173 NB1 Int.n-81 BRA6cHex H Me NO2 1Me-5-1HIdz C 437 (M⁺ + 1) N-g-174 NA N-g-173 cHex H H NO21Me-5-1HIdz C 423 (M⁺ + 1) N-g-175 NB1 Int.n-82 BRA1 2(Me)cHex H Me NO22-Nap C 447 (M⁺ + 1) N-g-176 NA N-g-175 2(Me)cHex H H NO2 2-Nap C 433(M⁺ + 1) N-g-177 NB1 Int.n-82 BRA2 2(Me)cHex H Me NO2 5-Ind C 436(M⁺ + 1) N-g-178 NA N-g-177 2(Me)cHex H H NO2 5-Ind C 422 (M⁺ + 1)N-g-179 NB1 Int.n-82 BRA3 2(Me)cHex H Me NO2 1Me-5-Ind C 450 (M⁺ + 1)N-g-180 NA N-g-179 2(Me)cHex H H NO2 1Me-5-Ind C 436 (M⁺ + 1) N-g-181NB1 Int.n-82 BRA5 2(Me)cHex H Me NO2 5-1HIdz C 437 (M⁺ + 1) N-g-182 NAN-g-181 2(Me)cHex H H NO2 5-1HIdz C 423 (M⁺ + 1) N-g-183 NB1 Int.n-82BRA6 2(Me)cHex H Me NO2 1Me-5-1HIdz C 451 (M⁺ + 1) N-g-184 NA N-g-1832(Me)cHex H H NO2 1Me-5-1HIdz C 437 (M⁺ + 1)

TABLE N-G-5 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-g-185 NB1 Int.n-86 BRA1 2-Indane Me Me NO2 2-Nap C 481 (M⁺ + 1)N-g-186 NA N-g-185 2-Indane Me H NO2 2-Nap C 467 (M⁺ + 1) N-g-187 NB1Int.n-86 BRA3 2-Indane Me Me NO2 1Me-5-Ind C 484 (M⁺ + 1) N-g-188 NAN-g-187 2-Indane Me H NO2 1Me-5-Ind C 470 (M⁺ + 1) N-g-189 NB1 Int.n-86BRA5 2-Indane Me Me NO2 5-1HIdz C 471 (M⁺ + 1) N-g-190 NA N-g-1892-Indane Me H NO2 5-1HIdz C 457 (M⁺ + 1) N-g-191 NB1 Int.n-86 BRA62-Indane Me Me NO2 1Me-5-1HIdz C 485 (M⁺ + 1) N-g-192 NA N-g-1912-Indane Me H NO2 1Me-5-1HIdz C 471 (M⁺ + 1) N-g-193 NB1 Int.n-87 BRA1cHex Me Me NO2 2-Nap C 447 (M⁺ + 1) N-g-194 NA N-g-193 cHex Me H NO22-Nap C 433 (M⁺ + 1) N-g-195 NB1 Int.n-87 BRA3 cHex Me Me NO2 1Me-5-IndC 450 (M⁺ + 1) N-g-196 NA N-g-195 cHex Me H NO2 1Me-5-Ind C 436 (M⁺ + 1)N-g-197 NB1 Int.n-87 BRA5 cHex Me Me NO2 5-1HIdz C 437 (M⁺ + 1) N-g-198NA N-g-197 cHex Me H NO2 5-1HIdz C 423 (M⁺ + 1) N-g-199 NB1 Int.n-87BRA6 cHex Me Me NO2 1Me-5-1HIdz C 451 (M⁺ + 1) N-g-200 NA N-g-199 cHexMe H NO2 1Me-5-1HIdz C 437 (M⁺ + 1) N-g-201 NB1 Int.n-88 BRA1 4(Me)cHexMe Me NO2 2-Nap C 461 (M⁺ + 1) N-g-202 NA N-g-201 4(Me)cHex Me H NO22-Nap C 447 (M⁺ + 1) N-g-203 NB1 Int.n-88 BRA3 4(Me)cHex Me Me NO21Me-5-Ind C 464 (M⁺ + 1) N-g-204 NA N-g-203 4(Me)cHex Me H NO2 1Me-5-IndC 450 (M⁺ + 1) N-g-205 NB1 Int.n-88 BRA6 4(Me)cHex Me Me NO2 1Me-5-1HIdzC 465 (M⁺ + 1) N-g-206 NA N-g-205 4(Me)cHex Me H NO2 1Me-5-1HIdz C 451(M⁺ + 1) N-g-207 ND1 N-g-159 2-Indane H Me NH2 5-Ind C 426 (M⁺ + 1)N-g-208 NA N-g-207 2-Indane H H NH2 5-Ind C 412 (M⁺ + 1) N-g-209 ND1N-g-161 2-Indane H Me NH2 1Me-5-Ind C 440 (M⁺ + 1) N-g-210 NA N-g-2092-Indane H H NH2 1Me-5-Ind C 426 (M⁺ + 1) N-g-211 ND1 N-g-163 2-Indane HMe NH2 5-1HIdz C 427 (M⁺ + 1) N-g-212 NA N-g-211 2-Indane H H NH25-1HIdz C 413 (M⁺ + 1) N-g-213 ND1 N-g-165 2-Indane H Me NH2 1Me-5-1HIdzC 441 (M⁺ + 1) N-g-214 NA N-g-213 2-Indane H H NH2 1Me-5-1HIdz C 427(M⁺ + 1) N-g-215 ND1 N-g-167 cHex H Me NH2 5-Ind C 392 (M⁺ + 1) N-g-216NA N-g-215 cHex H H NH2 5-Ind C 378 (M⁺ + 1) N-g-217 ND1 N-g-169 cHex HMe NH2 1Me-5-Ind C 406 (M⁺ + 1) N-g-218 NA N-g-217 cHex H H NH21Me-5-Ind C 392 (M⁺ + 1) N-g-219 ND1 N-g-171 cHex H Me NH2 5-1HIdz C 393(M⁺ + 1) N-g-220 NA N-g-219 cHex H H NH2 5-1HIdz C 379 (M⁺ + 1) N-g-221ND1 N-g-173 cHex H Me NH2 1Me-5-1HIdz C 407 (M⁺ + 1) N-g-222 NA N-g-221cHex H H NH2 1Me-5-1HIdz C 393 (M⁺ + 1) N-g-223 ND1 N-g-177 4(Me)cHex HMe NH2 5-Ind C 406 (M⁺ + 1) N-g-224 NA N-g-223 4(Me)cHex H H NH2 5-Ind C392 (M⁺ + 1) N-g-225 ND1 N-g-179 4(Me)cHex H Me NH2 1Me-5-Ind C 420(M⁺ + 1) N-g-226 NA N-g-225 4(Me)cHex H H NH2 1Me-5-Ind C 406 (M⁺ + 1)N-g-227 ND1 N-g-181 4(Me)cHex H Me NH2 5-1HIdz C 407 (M⁺ + 1) N-g-228 NAN-g-227 4(Me)cHex H H NH2 5-1HIdz C 393 (M⁺ + 1) N-g-229 ND1 N-g-1834(Me)cHex H Me NH2 1Me-5-1HIdz C 421 (M⁺ + 1) N-g-230 NA N-g-2294(Me)cHex H H NH2 1Me-5-1HIdz C 407 (M⁺ + 1)

TABLE N-G-6 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-g-231 ND1 N-g-185 2-Indane Me Me NH2 2-Nap C 451 (M⁺ + 1) N-g-232 NAN-g-231 2-Indane Me H NH2 2-Nap C 437 (M⁺ + 1) N-g-233 ND1 N-g-1872-Indane Me Me NH2 1Me-5-Ind C 454 (M⁺ + 1) N-g-234 NA N-g-233 2-IndaneMe H NH2 1Me-5-Ind C 440 (M⁺ + 1) N-g-235 ND1 N-g-191 2-Indane Me Me NH21Me-5-1HIdz C 455 (M⁺ + 1) N-g-236 NA N-g-235 2-Indane Me H NH21Me-5-1HIdz C 441 (M⁺ + 1) N-g-237 ND1 N-g-193 cHex Me Me NH2 2-Nap C417 (M⁺ + 1) N-g-238 NA N-g-237 cHex Me H NH2 2-Nap C 403 (M⁺ + 1)N-g-239 ND1 N-g-195 cHex Me Me NH2 1Me-5-Ind C 420 (M⁺ + 1) N-g-240 NAN-g-239 cHex Me H NH2 1Me-5-Ind C 406 (M⁺ + 1) N-g-241 ND1 N-g-197 cHexMe Me NH2 5-1HIdz C 407 (M⁺ + 1) N-g-242 NA N-g-241 cHex Me H NH25-1HIdz C 393 (M⁺ + 1) N-g-243 ND1 N-g-199 cHex Me Me NH2 1Me-5-1HIdz C421 (M⁺ + 1) N-g-244 NA N-g-243 cHex Me H NH2 1Me-5-1HIdz C 407 (M⁺ + 1)N-g-245 ND1 N-g-201 4(Me)cHex Me Me NH2 2-Nap C 431 (M⁺ + 1) N-g-246 NAN-g-245 4(Me)cHex Me H NH2 2-Nap C 417 (M⁺ + 1) N-g-247 ND1 N-g-2034(Me)cHex Me Me NH2 1Me-5-Ind C 434 (M⁺ + 1) N-g-248 NA N-g-2474(Me)cHex Me H NH2 1Me-5-Ind C 420 (M⁺ + 1) N-g-249 ND1 N-g-2054(Me)cHex Me Me NH2 1Me-5-1HIdz C 435 (M⁺ + 1) N-g-250 NA N-g-2494(Me)cHex Me H NH2 1Me-5-1HIdz C 421 (M⁺ + 1) N-g-251 NN1 N-g-131 CH₃IcPen Me Me NHMe 2-Nap C 417 (M⁺ + 1) N-g-252 NA N-g-251 cPen Me H NHMe2-Nap C 403 (M⁺ + 1) N-g-253 NN1 N-g-133 CH₃I cPen Me Me NHMe 1Me-5-IndC 420 (M⁺ + 1) N-g-254 NA N-g-253 cPen Me H NHMe 1Me-5-Ind C 406(M⁺ + 1) N-g-255 NN1 N-g-137 CH₃I cPen Me Me NHMe 1Me-5-1HIdz C 421(M⁺ + 1) N-g-256 NA N-g-255 cPen Me H NHMe 1Me-5-1HIdz C 407 (M⁺ + 1)N-g-257 NN1 N-g-139 CH₃I nPr Me Me NHMe 2-Nap C 391 (M⁺ + 1) N-g-258 NAN-g-257 nPr Me H NHMe 2-Nap C 377 (M⁺ + 1) N-g-259 NN1 N-g-143 CH₃I nPrMe Me NHMe 1Me-5-Ind C 394 (M⁺ + 1) N-g-260 NA N-g-259 nPr Me H NHMe1Me-5-Ind C 380 (M⁺ + 1) N-g-261 NN1 N-g-147 CH₃I nPr Me Me NHMe1Me-5-1HIdz C 395 (M⁺ + 1) N-g-262 NA N-g-261 nPr Me H NHMe 1Me-5-1HIdzC 381 (M⁺ + 1) N-g-263 NN1 N-g-149 CH₃I iPr Me Me NHMe 2-Nap C 391(M⁺ + 1) N-g-264 NA N-g-263 iPr Me H NHMe 2-Nap C 377 (M⁺ + 1) N-g-265NN1 N-g-151 CH₃I iPr Me Me NHMe 1Me-5-Ind C 394 (M⁺ + 1) N-g-266 NAN-g-265 iPr Me H NHMe 1Me-5-Ind C 380 (M⁺ + 1) N-g-267 NN1 N-g-155 CH₃IiPr Me Me NHMe 1Me-5-1HIdz C 395 (M⁺ + 1) N-g-268 NA N-g-267 iPr Me HNHMe 1Me-5-1HIdz C 381 (M⁺ + 1) N-g-269 NN1 N-g-231 CH₃I 2-Indane Me MeNHMe 2-Nap C 465 (M⁺ + 1) N-g-270 NA N-g-269 2-Indane Me H NHMe 2-Nap C451 (M⁺ + 1) N-g-271 NN1 N-g-233 CH₃I 2-Indane Me Me NHMe 1Me-5-Ind C468 (M⁺ + 1) N-g-272 NA N-g-271 2-Indane Me H NHMe 1Me-5-Ind C 454(M⁺ + 1) N-g-273 NN1 N-g-235 CH₃I 2-Indane Me Me NHMe 1Me-5-1HIdz C 469(M⁺ + 1) N-g-274 NA N-g-273 2-Indane Me H NHMe 1Me-5-1HIdz C 455(M⁺ + 1) N-g-275 NN1 N-g-237 CH₃I cHex Me Me NHMe 2-Nap C 431 (M⁺ + 1)N-g-276 NA N-g-275 cHex Me H NHMe 2-Nap C 417 (M⁺ + 1)

TABLE N-G-7 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-g-277 NN1 N-g-239 CH₃I cHex Me Me NHMe 1Me-5-Ind C 434 (M⁺ + 1)N-g-278 NA N-g-277 cHex Me H NHMe 1Me-5-Ind C 420 (M⁺ + 1) N-g-279 NN1N-g-245 CH₃I 4Me-cHex Me Me NHMe 2-Nap C 445 (M⁺ + 1) N-g-280 NA N-g-2794Me-cHex Me H NHMe 2-Nap C 431 (M⁺ + 1) N-g-281 NN2 N-g-247 CH₃I4Me-cHex Me Me NMe₂ 1Me-5-Ind C 448 (M⁺ + 1) N-g-282 NA N-g-281 4Me-cHexMe H NMe₂ 1Me-5-Ind C 434 (M⁺ + 1) N-g-283 NN2 N-g-249 CH₃I 4Me-cHex MeMe NMe₂ 1Me-5-1HIdz C 449 (M⁺ + 1) N-g-284 NA N-g-283 4Me-cHex Me H NMe₂1Me-5-1HIdz C 435 (M⁺ + 1) N-g-285 NN2 N-g-131 CH₃I cPen Me Me NMe₂2-Nap C 431 (M⁺ + 1) N-g-286 NA N-g-285 cPen Me H NMe₂ 2-Nap C 417(M⁺ + 1) N-g-287 NN2 N-g-133 CH₃I cPen Me Me NMe₂ 1Me-5-Ind C 434(M⁺ + 1) N-g-288 NA N-g-287 cPen Me H NMe₂ 1Me-5-Ind C 420 (M⁺ + 1)N-g-289 NN2 N-g-137 CH₃I cPen Me Me NMe₂ 1Me-5-1HIdz C 435 (M⁺ + 1)N-g-290 NA N-g-289 cPen Me H NMe₂ 1Me-5-1HIdz C 421 (M⁺ + 1) N-g-291 NN2N-g-139 CH₃I nPr Me Me NMe₂ 2-Nap C 405 (M⁺ + 1) N-g-292 NA N-g-291 nPrMe H NMe₂ 2-Nap C 391 (M⁺ + 1) N-g-293 NN2 N-g-143 CH₃I nPr Me Me NMe₂1Me-5-Ind C 408 (M⁺ + 1) N-g-294 NA N-g-293 nPr Me H NMe₂ 1Me-5-Ind C394 (M⁺ + 1) N-g-295 NN2 N-g-147 CH₃I nPr Me Me NMe₂ 1Me-5-1HIdz C 409(M⁺ + 1) N-g-296 NA N-g-295 nPr Me H NMe₂ 1Me-5-1HIdz C 395 (M⁺ + 1)N-g-297 NN2 N-g-149 CH₃I iPr Me Me NMe₂ 2-Nap C 405 (M⁺ + 1) N-g-298 NAN-g-297 iPr Me H NMe₂ 2-Nap C 391 (M⁺ + 1) N-g-299 NN2 N-g-151 CH₃I iPrMe Me NMe₂ 1Me-5-Ind C 408 (M⁺ + 1) N-g-300 NA N-g-299 iPr Me H NMe₂1Me-5-Ind C 394 (M⁺ + 1) N-g-301 NN2 N-g-155 CH₃I iPr Me Me NMe₂1Me-5-1HIdz C 409 (M⁺ + 1) N-g-302 NA N-g-301 iPr Me H NMe₂ 1Me-5-1HIdzC 395 (M⁺ + 1) N-g-303 NN2 N-g-231 CH₃I 2Indane Me Me NMe₂ 2-Nap C 479(M⁺ + 1) N-g-304 NA N-g-303 2Indane Me H NMe₂ 2-Nap C 465 (M⁺ + 1)N-g-305 NN2 N-g-233 CH₃I 2Indane Me Me NMe₂ 1Me-5-Ind C 482 (M⁺ + 1)N-g-306 NA N-g-305 2Indane Me H NMe₂ 1Me-5-Ind C 468 (M⁺ + 1) N-g-307NN2 N-g-235 CH₃I 2Indane Me Me NMe₂ 1Me-5-1HIdz C 483 (M⁺ + 1) N-g-308NA N-g-307 2Indane Me H NMe₂ 1Me-5-1HIdz C 469 (M⁺ + 1) N-g-309 NN2N-g-237 CH₃I cHex Me Me NMe₂ 2-Nap C 445 (M⁺ + 1) N-g-310 NA N-g-265cHex Me H NMe₂ 2-Nap C 431 (M⁺ + 1) N-g-311 NN2 N-g-239 CH₃I cHex Me MeNMe₂ 1Me-5-Ind C 448 (M⁺ + 1) N-g-312 NA N-g-267 cHex Me H NMe₂1Me-5-Ind C 434 (M⁺ + 1) N-g-313 NN2 N-g-245 CH₃I 4Me-cHex Me Me NMe₂2-Nap C 459 (M⁺ + 1) N-g-314 NA N-g-269 4Me-cHex Me H NMe₂ 2-Nap C 445(M⁺ + 1) N-g-315 NN2 N-g-247 CH₃I 4Me-cHex Me Me NMe₂ 1Me-5-Ind C 462(M⁺ + 1) N-g-316 NA N-g-271 4Me-cHex Me H NMe₂ 1Me-5-Ind C 448 (M⁺ + 1)N-g-317 NN2 N-g-249 CH₃I 4Me-cHex Me Me NMe₂ 1Me-5-1HIdz C 463 (M⁺ + 1)N-g-318 NA N-g-273 4Me-cHex Me H NMe₂ 1Me-5-1HIdz C 449 (M⁺ + 1)

Examples N-h-1 to N-h-458

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification are shown inTable-N-H-1 to Table-N-H-10. In the tables, the compound numbers arementioned in the columns indicated as “Exp.”. In the tables,corresponding methods among the aforementioned synthesis methods areshown in the columns of “Syn” with symbols, the starting compounds 1 arementioned in the columns of “SM1”, and the starting compounds 2 arementioned in the columns of “SM2”.

TABLE-N-H-1

LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-h-1 NB1 Int.n-89BRA1 Bn H Me NO2 2-Nap C 441 (M⁺ + 1) N-h-2 NA N-h-1 Bn H H NO2 2-Nap C427 (M⁺ + 1) N-h-3 NB1 Int.n-89 BRA2 Bn H Me NO2 5-Ind C 430 (M⁺ + 1)N-h-4 NA N-h-3 Bn H H NO2 5-Ind C 416 (M⁺ + 1) N-h-5 NB1 Int.n-89 BRA3Bn H Me NO2 1Me-5-Ind C 444 (M⁺ + 1) N-h-6 NA N-h-5 Bn H H NO2 1Me-5-IndC 430 (M⁺ + 1) N-h-7 NB1 Int.n-89 BRA5 Bn H Me NO2 5-1HIdz C 431(M⁺ + 1) N-h-8 NA N-h-7 Bn H H NO2 5-1HIdz C 417 (M⁺ + 1) N-h-9 NB1Int.n-89 BRA6 Bn H Me NO2 1Me-5-1HIdz C 445 (M⁺ + 1) N-h-10 NA N-h-9 BnH H NO2 1Me-5-1HIdz C 431 (M⁺ + 1) N-h-11 NB1 Int.n-89 BRA10 Bn H Me NO23-Qu C 442 (M⁺ + 1) N-h-12 NA N-h-11 Bn H H NO2 3-Qu C 428 (M⁺ + 1)N-h-13 NB1 Int.n-89 BRA11 Bn H Me NO2 6-Qu C 442 (M⁺ + 1) N-h-14 NAN-h-13 Bn H H NO2 6-Qu C 428 (M⁺ + 1) N-h-15 NB1 Int.n-89 BRA12 Bn H MeNO2 6-IQ C 442 (M⁺ + 1) N-h-16 NA N-h-15 Bn H H NO2 6-IQ C 428 (M⁺ + 1)N-h-17 NB1 Int.n-90 BRA1 4FBn H Me NO2 2-Nap C 459 (M⁺ + 1) N-h-18 NAN-h-17 4FBn H H NO2 2-Nap C 445 (M⁺ + 1) N-h-19 NB1 Int.n-90 BRA2 4FBn HMe NO2 5-Ind C 448 (M⁺ + 1) N-h-20 NA N-h-19 4FBn H H NO2 5-Ind C 434(M⁺ + 1) N-h-21 NB1 Int.n-90 BRA3 4FBn H Me NO2 1Me-5-Ind C 462 (M⁺ + 1)N-h-22 NA N-h-21 4FBn H H NO2 1Me-5-Ind C 448 (M⁺ + 1) N-h-23 NB1Int.n-90 BRA5 4FBn H Me NO2 5-1HIdz C 449 (M⁺ + 1) N-h-24 NA N-h-23 4FBnH H NO2 5-1HIdz C 435 (M⁺ + 1) N-h-25 NB1 Int.n-90 BRA6 4FBn H Me NO21Me-5-1HIdz C 463 (M⁺ + 1) N-h-26 NA N-h-25 4FBn H H NO2 1Me-5-1HIdz C449 (M⁺ + 1) N-h-27 NB1 Int.n-91 BRA2 2FBn H Me NO2 5-Ind C 448 (M⁺ + 1)N-h-28 NA N-h-27 2FBn H H NO2 5-Ind C 434 (M⁺ + 1) N-h-29 NB1 Int.n-91BRA3 2FBn H Me NO2 1Me-5-Ind C 462 (M⁺ + 1) N-h-30 NA N-h-29 2FBn H HNO2 1Me-5-Ind C 448 (M⁺ + 1) N-h-31 NB1 Int.n-91 BRA5 2FBn H Me NO25-1HIdz C 449 (M⁺ + 1) N-h-32 NA N-h-31 2FBn H H NO2 5-1HIdz C 435(M⁺ + 1) N-h-33 NB1 Int.n-91 BRA6 2FBn H Me NO2 1Me-5-1HIdz C 463(M⁺ + 1) N-h-34 NA N-h-33 2FBn H H NO2 1Me-5-1HIdz C 449 (M⁺ + 1) N-h-35NB1 Int.n-92 BRA2 3FBn H Me NO2 5-Ind C 448 (M⁺ + 1) N-h-36 NA N-h-353FBn H H NO2 5-Ind C 434 (M⁺ + 1) N-h-37 NB1 Int.n-92 BRA3 3FBn H Me NO21Me-5-Ind C 462 (M⁺ + 1) N-h-38 NA N-h-37 3FBn H H NO2 1Me-5-Ind C 448(M⁺ + 1) N-h-39 NB1 Int.n-92 BRA5 3FBn H Me NO2 5-1HIdz C 449 (M⁺ + 1)N-h-40 NA N-h-39 3FBn H H NO2 5-1HIdz C 435 (M⁺ + 1) N-h-41 NB1 Int.n-92BRA6 3FBn H Me NO2 1Me-5-1HIdz C 463 (M⁺ + 1) N-h-42 NA N-h-41 3FBn H HNO2 1Me-5-1HIdz C 449 (M⁺ + 1) N-h-43 NB1 Int.n-93 BRA1 2,3DFBn H Me NO22-Nap C 477 (M⁺ + 1) N-h-44 NA N-h-43 2,3DFBn H H NO2 2-Nap C 463(M⁺ + 1) N-h-45 NB1 Int.n-93 BRA3 2,3DFBn H Me NO2 1Me-5-Ind C 480(M⁺ + 1) N-h-46 NA N-h-45 2,3DFBn H H NO2 1Me-5-Ind C 466 (M⁺ + 1)

TABLE N-H-2 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-h-47NB1 Int.n-93 BRA5 2,3DFBn H Me NO2 5-1HIdz C 467 (M⁺ + 1) N-h-48 NAN-h-47 2,3DFBn H H NO2 5-1HIdz C 453 (M⁺ + 1) N-h-49 NB1 Int.n-93 BRA62,3DFBn H Me NO2 1Me-5-1HIdz C 481 (M⁺ + 1) N-h-50 NA N-h-49 2,3DFBn H HNO2 1Me-5-1HIdz C 467 (M⁺ + 1) N-h-51 NB1 Int.n-94 BRA2 3,4DFBn H Me NO25-Ind C 466 (M⁺ + 1) N-h-52 NA N-h-51 3,4DFBn H H NO2 5-Ind C 452(M⁺ + 1) N-h-53 NB1 Int.n-94 BRA3 3,4DFBn H Me NO2 1Me-5-Ind C 480(M⁺ + 1) N-h-54 NA N-h-53 3,4DFBn H H NO2 1Me-5-Ind C 466 (M⁺ + 1)N-h-55 NB1 Int.n-94 BRA6 3,4DFBn H Me NO2 1Me-5-1HIdz C 481 (M⁺ + 1)N-h-56 NA N-h-55 3,4DFBn H H NO2 1Me-5-1HIdz C 467 (M⁺ + 1) N-h-57 NB1Int.n-95 BRA1 4PhBn H Me NO2 2-Nap C 517 (M⁺ + 1) N-h-58 NA N-h-57 4PhBnH H NO2 2-Nap C 503 (M⁺ + 1) N-h-59 NB1 Int.n-95 BRA2 4PhBn H Me NO25-Ind C 506 (M⁺ + 1) N-h-60 NA N-h-59 4PhBn H H NO2 5-Ind C 492 (M⁺ + 1)N-h-61 NB1 Int.n-95 BRA3 4PhBn H Me NO2 1Me-5-Ind C 520 (M⁺ + 1) N-h-62NA N-h-61 4PhBn H H NO2 1Me-5-Ind C 506 (M⁺ + 1) N-h-63 NB1 Int.n-95BRA5 4PhBn H Me NO2 5-1HIdz C 507 (M⁺ + 1) N-h-64 NA N-h-63 4PhBn H HNO2 5-1HIdz C 493 (M⁺ + 1) N-h-65 NB1 Int.n-96 BRA1 2CF3Bn H Me NO22-Nap C 509 (M⁺ + 1) N-h-66 NA N-h-65 2CF3Bn H H NO2 2-Nap C 495(M⁺ + 1) N-h-67 NB1 Int.n-96 BRA2 2CF3Bn H Me NO2 5-Ind C 498 (M⁺ + 1)N-h-68 NA N-h-67 2CF3Bn H H NO2 5-Ind C 484 (M⁺ + 1) N-h-69 NB1 Int.n-96BRA3 2CF3Bn H Me NO2 1Me-5-Ind C 512 (M⁺ + 1) N-h-70 NA N-h-69 2CF3Bn HH NO2 1Me-5-Ind C 498 (M⁺ + 1) N-h-71 NB1 Int.n-96 BRA5 2CF3Bn H Me NO25-1HIdz C 499 (M⁺ + 1) N-h-72 NA N-h-71 2CF3Bn H H NO2 5-1HIdz C 485(M⁺ + 1) N-h-73 NB1 Int.n-97 BRA2 2-TF H Me NO2 5-Ind C 436 (M⁺ + 1)N-h-74 NA N-h-73 2-TF H H NO2 5-Ind C 422 (M⁺ + 1) N-h-75 NB1 Int.n-97BRA3 2-TF H Me NO2 1Me-5-Ind C 450 (M⁺ + 1) N-h-76 NA N-h-75 2-TF H HNO2 1Me-5-Ind C 436 (M⁺ + 1) N-h-77 NB1 Int.n-97 BRA6 2-TF H Me NO21Me-5-1HIdz C 451 (M⁺ + 1) N-h-78 NA N-h-77 2-TF H H NO2 1Me-5-1HIdz C437 (M⁺ + 1) N-h-79 NB1 Int.n-98 BRA2 3-TF H Me NO2 5-Ind C 436 (M⁺ + 1)N-h-80 NA N-h-79 3-TF H H NO2 5-Ind C 422 (M⁺ + 1) N-h-81 NB1 Int.n-98BRA3 3-TF H Me NO2 1Me-5-Ind C 450 (M⁺ + 1) N-h-82 NA N-h-81 3-TF H HNO2 1Me-5-Ind C 436 (M⁺ + 1) N-h-83 NB1 Int.n-98 BRA5 3-TF H Me NO25-1HIdz C 437 (M⁺ + 1) N-h-84 NA N-h-83 3-TF H H NO2 5-1HIdz C 423(M⁺ + 1) N-h-85 NB1 Int.n-98 BRA6 3-TF H Me NO2 1Me-5-1HIdz C 451(M⁺ + 1) N-h-86 NA N-h-85 3-TF H H NO2 1Me-5-1HIdz C 437 (M⁺ + 1) N-h-87NB1 Int.n-99 BRA1 2-FR H Me NO2 2Nap C 459 (M⁺ + 1) N-h-88 NA N-h-872-FR H H NO2 2Nap C 445 (M⁺ + 1) N-h-89 NB1 Int.n-99 BRA2 2-FR H Me NO25-Ind C 420 (M⁺ + 1) N-h-90 NA N-h-89 2-FR H H NO2 5-Ind C 406 (M⁺ + 1)N-h-91 NB1 Int.n-99 BRA6 2-FR H Me NO2 1Me-5-1HIdz C 434 (M⁺ + 1) N-h-92NA N-h-91 2-FR H H NO2 1Me-5-1HIdz C 420 (M⁺ + 1)

TABLE N-H-3 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime Mass N-h-93NB1 Int.n-100 BRA1 Bn Me Me NO2 2-Nap C 455 (M⁺ + 1) N-h-94 NA N-h-93 BnMe H NO2 2-Nap C 427 (M⁺ + 1) N-h-95 NB1 Int.n-100 BRA2 Bn Me Me NO25-Ind C 430 (M⁺ + 1) N-h-96 NA N-h-95 Bn Me H NO2 5-Ind C 416 (M⁺ + 1)N-h-97 NB1 Int.n-100 BRA3 Bn Me Me NO2 1Me-5-Ind C 444 (M⁺ + 1) N-h-98NA N-h-97 Bn Me H NO2 1Me-5-Ind C 430 (M⁺ + 1) N-h-99 NB1 Int.n-100 BRA5Bn Me Me NO2 5-1HIdz C 431 (M⁺ + 1) N-h-100 NA N-h-99 Bn Me H NO25-1HIdz C 417 (M⁺ + 1) N-h-101 NB1 Int.n-100 BRA6 Bn Me Me NO21Me-5-1HIdz C 445 (M⁺ + 1) N-h-102 NA N-h-101 Bn Me H NO2 1Me-5-1HIdz C431 (M⁺ + 1) N-h-103 NB1 Int.n-100 BRA10 Bn Me Me NO2 3-Qu C 442(M⁺ + 1) N-h-104 NA N-h-103 Bn Me H NO2 3-Qu C 428 (M⁺ + 1) N-h-105 NB1Int.n-100 BRA11 Bn Me Me NO2 6-Qu C 442 (M⁺ + 1) N-h-106 NA N-h-105 BnMe H NO2 6-Qu C 428 (M⁺ + 1) N-h-107 NB1 Int.n-100 BRA12 Bn Me Me NO26-IQ C 442 (M⁺ + 1) N-h-108 NA N-h-107 Bn Me H NO2 6-IQ C 428 (M⁺ + 1)N-h-109 NB1 Int.n-101 BRA1 4FBn Me Me NO2 2-Nap C 459 (M⁺ + 1) N-h-110NA N-h-109 4FBn Me H NO2 2-Nap C 445 (M⁺ + 1) N-h-111 NB1 Int.n-101 BRA24FBn Me Me NO2 5-Ind C 448 (M⁺ + 1) N-h-112 NA N-h-111 4FBn Me H NO25-Ind C 434 (M⁺ + 1) N-h-113 NB1 Int.n-101 BRA3 4FBn Me Me NO2 1Me-5-IndC 462 (M⁺ + 1) N-h-114 NA N-h-113 4FBn Me H NO2 1Me-5-Ind C 448 (M⁺ + 1)N-h-115 NB1 Int.n-101 BRA5 4FBn Me Me NO2 5-1HIdz C 449 (M⁺ + 1) N-h-116NA N-h-115 4FBn Me H NO2 5-1HIdz C 435 (M⁺ + 1) N-h-117 NB1 Int.n-101BRA6 4FBn Me Me NO2 1Me-5-1HIdz C 463 (M⁺ + 1) N-h-118 NA N-h-117 4FBnMe H NO2 1Me-5-1HIdz C 449 (M⁺ + 1) N-h-119 NB1 Int.n-102 BRA1 2FBn MeMe NO2 2-Nap C 448 (M⁺ + 1) N-h-120 NA N-h-119 2FBn Me H NO2 2-Nap C 434(M⁺ + 1) N-h-121 NB1 Int.n-102 BRA3 2FBn Me Me NO2 1Me-5-Ind C 462(M⁺ + 1) N-h-122 NA N-h-121 2FBn Me H NO2 1Me-5-Ind C 448 (M⁺ + 1)N-h-123 NB1 Int.n-102 BRA5 2FBn Me Me NO2 5-1HIdz C 449 (M⁺ + 1) N-h-124NA N-h-123 2FBn Me H NO2 5-1HIdz C 435 (M⁺ + 1) N-h-125 NB1 Int.n-102BRA6 2FBn Me Me NO2 1Me-5-1HIdz C 463 (M⁺ + 1) N-h-126 NA N-h-125 2FBnMe H NO2 1Me-5-1HIdz C 449 (M⁺ + 1) N-h-127 NB1 Int.n-103 BRA1 3FBn MeMe NO2 2-Nap C 448 (M⁺ + 1) N-h-128 NA N-h-127 3FBn Me H NO2 2-Nap C 434(M⁺ + 1) N-h-129 NB1 Int.n-103 BRA3 3FBn Me Me NO2 1Me-5-Ind C 462(M⁺ + 1) N-h-130 NA N-h-129 3FBn Me H NO2 1Me-5-Ind C 448 (M⁺ + 1)N-h-131 NB1 Int.n-103 BRA5 3FBn Me Me NO2 5-1HIdz C 449 (M⁺ + 1) N-h-132NA N-h-131 3FBn Me H NO2 5-1HIdz C 435 (M⁺ + 1) N-h-133 NB1 Int.n-103BRA6 3FBn Me Me NO2 1Me-5-1HIdz C 463 (M⁺ + 1) N-h-134 NA N-h-133 3FBnMe H NO2 1Me-5-1HIdz C 449 (M⁺ + 1) N-h-135 NB1 Int.n-104 BRA1 2,3DFBnMe Me NO2 2-Nap C 477 (M⁺ + 1) N-h-136 NA N-h-135 2,3DFBn Me H NO2 2-NapC 463 (M⁺ + 1) N-h-137 NB1 Int.n-104 BRA3 2,3DFBn Me Me NO2 1Me-5-Ind C480 (M⁺ + 1) N-h-138 NA N-h-137 2,3DFBn Me H NO2 1Me-5-Ind C 466 (M⁺ +1)

TABLE N-H-4 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-h-139 NB1 Int.n-104 BRA5 2,3DFBn Me Me NO2 5-1HIdz C 481 (M⁺ + 1)N-h-140 NA N-h-139 2,3DFBn Me H NO2 5-1HIdz C 467 (M⁺ + 1) N-h-141 NB1Int.n-104 BRA6 2,3DFBn Me Me NO2 1Me-5-1HIdz C 495 (M⁺ + 1) N-h-142 NAN-h-141 2,3DFBn Me H NO2 1Me-5-1HIdz C 481 (M⁺ + 1) N-h-143 NB1Int.n-105 BRA1 3,4DFBn Me Me NO2 2-Nap C 480 (M⁺ + 1) N-h-144 NA N-h-1433,4DFBn Me H NO2 2-Nap C 466 (M⁺ + 1) N-h-145 NB1 Int.n-105 BRA3 3,4DFBnMe Me NO2 1Me-5-Ind C 494 (M⁺ + 1) N-h-146 NA N-h-145 3,4DFBn Me H NO21Me-5-Ind C 480 (M⁺ + 1) N-h-147 NB1 Int.n-105 BRA6 3,4DFBn Me Me NO21Me-5-1HIdz C 495 (M⁺ + 1) N-h-148 NA N-h-147 3,4DFBn Me H NO21Me-5-1HIdz C 481 (M⁺ + 1) N-h-149 NB1 Int.n-106 BRA1 4PhBn Me Me NO22-Nap C 531 (M⁺ + 1) N-h-150 NA N-h-149 4PhBn Me H NO2 2-Nap C 517(M⁺ + 1) N-h-151 NB1 Int.n-106 BRA2 4PhBn Me Me NO2 5-Ind C 520 (M⁺ + 1)N-h-152 NA N-h-151 4PhBn Me H NO2 5-Ind C 506 (M⁺ + 1) N-h-153 NB1Int.n-106 BRA3 4PhBn Me Me NO2 1Me-5-Ind C 534 (M⁺ + 1) N-h-154 NAN-h-153 4PhBn Me H NO2 1Me-5-Ind C 520 (M⁺ + 1) N-h-155 NB1 Int.n-106BRA6 4PhBn Me Me NO2 1Me-5-1HIdz C 521 (M⁺ + 1) N-h-156 NA N-h-155 4PhBnMe H NO2 1Me-5-1HIdz C 507 (M⁺ + 1) N-h-157 NB1 Int.n-107 BRA1 2CF3Bn MeMe NO2 2-Nap C 523 (M⁺ + 1) N-h-158 NA N-h-157 2CF3Bn Me H NO2 2-Nap C509 (M⁺ + 1) N-h-159 NB1 Int.n-107 BRA2 2CF3Bn Me Me NO2 5-Ind C 512(M⁺ + 1) N-h-160 NA N-h-159 2CF3Bn Me H NO2 5-Ind C 498 (M⁺ + 1) N-h-161NB1 Int.n-107 BRA3 2CF3Bn Me Me NO2 1Me-5-Ind C 526 (M⁺ + 1) N-h-162 NAN-h-161 2CF3Bn Me H NO2 1Me-5-Ind C 512 (M⁺ + 1) N-h-163 NB1 Int.n-107BRA5 2CF3Bn Me Me NO2 5-1HIdz C 513 (M⁺ + 1) N-h-164 NA N-h-163 2CF3BnMe H NO2 5-1HIdz C 499 (M⁺ + 1) N-h-165 NB1 Int.n-108 BRA1 2-TF Me MeNO2 2-Nap C 450 (M⁺ + 1) N-h-166 NA N-h-165 2-TF Me H NO2 2-Nap C 436(M⁺ + 1) N-h-167 NB1 Int.n-108 BRA3 2-TF Me Me NO2 1Me-5-Ind C 464(M⁺ + 1) N-h-168 NA N-h-167 2-TF Me H NO2 1Me-5-Ind C 450 (M⁺ + 1)N-h-169 NB1 Int.n-108 BRA6 2-TF Me Me NO2 1Me-5-1HIdz C 465 (M⁺ + 1)N-h-170 NA N-h-169 2-TF Me H NO2 1Me-5-1HIdz C 451 (M⁺ + 1) N-h-171 NB1Int.n-109 BRA1 3-TF Me Me NO2 2-Nap C 450 (M⁺ + 1) N-h-172 NA N-h-1713-TF Me H NO2 2-Nap C 436 (M⁺ + 1) N-h-173 NB1 Int.n-109 BRA2 3-TF Me MeNO2 5-Ind C 464 (M⁺ + 1) N-h-174 NA N-h-173 3-TF Me H NO2 5-Ind C 450(M⁺ + 1) N-h-175 NB1 Int.n-109 BRA3 3-TF Me Me NO2 1Me-5-Ind C 451(M⁺ + 1) N-h-176 NA N-h-175 3-TF Me H NO2 1Me-5-Ind C 437 (M⁺ + 1)N-h-177 NB1 Int.n-110 BRA6 3-TF Me Me NO2 1Me-5-1HIdz C 465 (M⁺ + 1)N-h-178 NA N-h-177 3-TF Me H NO2 1Me-5-1HIdz C 451 (M⁺ + 1) N-h-179 NB1Int.n-110 BRA1 2-FR Me Me NO2 2-Nap C 473 (M⁺ + 1) N-h-180 NA N-h-1792-FR Me H NO2 2-Nap C 459 (M⁺ + 1) N-h-181 NB1 Int.n-110 BRA2 2-FR Me MeNO2 5-Ind C 434 (M⁺ + 1) N-h-182 NA N-h-181 2-FR Me H NO2 5-Ind C 420(M⁺ + 1) N-h-183 NB1 Int.n-109 BRA6 2-FR Me Me NO2 1Me-5-1HIdz C 448(M⁺ + 1) N-h-184 NA N-h-183 2-FR Me H NO2 1Me-5-1HIdz C 434 (M⁺ + 1)

TABLE N-H-5 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-h-185 ND1 N-h-1 Bn H Me NH2 2-Nap C 411 (M⁺ + 1) N-h-186 NA N-h-185 BnH H NH2 2-Nap C 397 (M⁺ + 1) N-h-187 ND1 N-h-3 Bn H Me NH2 5-Ind C 400(M⁺ + 1) N-h-188 NA N-h-187 Bn H H NH2 5-Ind C 386 (M⁺ + 1) N-h-189 ND1N-h-5 Bn H Me NH2 1Me-5-Ind C 414 (M⁺ + 1) N-h-190 NA N-h-189 Bn H H NH21Me-5-Ind C 400 (M⁺ + 1) N-h-191 ND1 N-h-7 Bn H Me NH2 5-1HIdz C 401(M⁺ + 1) N-h-192 NA N-h-191 Bn H H NH2 5-1HIdz C 387 (M⁺ + 1) N-h-193ND1 N-h-9 Bn H Me NH2 1Me-5-1HIdz C 415 (M⁺ + 1) N-h-194 NA N-h-193 Bn HH NH2 1Me-5-1HIdz C 401 (M⁺ + 1) N-h-195 ND1 N-h-11 Bn H Me NH2 3-Qu C412 (M⁺ + 1) N-h-196 NA N-h-195 Bn H H NH2 3-Qu C 398 (M⁺ + 1) N-h-197ND1 N-h-13 Bn H Me NH2 6-Qu C 412 (M⁺ + 1) N-h-198 NA N-h-197 Bn H H NH26-Qu C 398 (M⁺ + 1) N-h-199 ND1 N-h-17 4FBn H Me NH2 2-Nap C 429(M⁺ + 1) N-h-200 NA N-h-199 4FBn H H NH2 2-Nap C 415 (M⁺ + 1) N-h-201ND1 N-h-19 4FBn H Me NH2 5-Ind C 418 (M⁺ + 1) N-h-202 NA N-h-201 4FBn HH NH2 5-Ind C 404 (M⁺ + 1) N-h-203 ND1 N-h-21 4FBn H Me NH2 1Me-5-Ind C432 (M⁺ + 1) N-h-204 NA N-h-203 4FBn H H NH2 1Me-5-Ind C 418 (M⁺ + 1)N-h-205 ND1 N-h-23 4FBn H Me NH2 5-1HIdz C 419 (M⁺ + 1) N-h-206 NAN-h-205 4FBn H H NH2 5-1HIdz C 405 (M⁺ + 1) N-h-207 ND1 N-h-25 4FBn H MeNH2 1Me-5-1HIdz C 433 (M⁺ + 1) N-h-208 NA N-h-207 4FBn H H NH21Me-5-1HIdz C 419 (M⁺ + 1) N-h-209 ND1 N-h-27 2FBn H Me NH2 5-Ind C 418(M⁺ + 1) N-h-210 NA N-h-209 2FBn H H NH2 5-Ind C 404 (M⁺ + 1) N-h-211ND1 N-h-29 2FBn H Me NH2 1Me-5-Ind C 432 (M⁺ + 1) N-h-212 NA N-h-2112FBn H H NH2 1Me-5-Ind C 418 (M⁺ + 1) N-h-213 ND1 N-h-31 2FBn H Me NH25-1HIdz C 419 (M⁺ + 1) N-h-214 NA N-h-213 2FBn H H NH2 5-1HIdz C 405(M⁺ + 1) N-h-215 ND1 N-h-33 2FBn H Me NH2 1Me-5-1HIdz C 433 (M⁺ + 1)N-h-216 NA N-h-215 2FBn H H NH2 1Me-5-1HIdz C 419 (M⁺ + 1) N-h-217 ND1N-h-35 3FBn H Me NH2 5-Ind C 418 (M⁺ + 1) N-h-218 NA N-h-217 3FBn H HNH2 5-Ind C 404 (M⁺ + 1) N-h-219 ND1 N-h-37 3FBn H Me NH2 1Me-5-Ind C432 (M⁺ + 1) N-h-220 NA N-h-219 3FBn H H NH2 1Me-5-Ind C 418 (M⁺ + 1)N-h-221 ND1 N-h-39 3FBn H Me NH2 5-1HIdz C 419 (M⁺ + 1) N-h-222 NAN-h-221 3FBn H H NH2 5-1HIdz C 405 (M⁺ + 1) N-h-223 ND1 N-h-41 3FBn H MeNH2 1Me-5-1HIdz C 433 (M⁺ + 1) N-h-224 NA N-h-223 3FBn H H NH21Me-5-1HIdz C 419 (M⁺ + 1) N-h-225 ND1 N-h-43 2,3DFBn H Me NH2 2-Nap C447 (M⁺ + 1) N-h-226 NA N-h-225 2,3DFBn H H NH2 2-Nap C 433 (M⁺ + 1)N-h-227 ND1 N-h-45 2,3DFBn H Me NH2 1Me-5-Ind C 450 (M⁺ + 1) N-h-228 NAN-h-227 2,3DFBn H H NH2 1Me-5-Ind C 436 (M⁺ + 1) N-h-229 ND1 N-h-472,3DFBn H Me NH2 5-1HIdz C 437 (M⁺ + 1) N-h-230 NA N-h-229 2,3DFBn H HNH2 5-1HIdz C 423 (M⁺ + 1)

TABLE N-H-6 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-h-231 ND1 N-h-49 2,3DFBn H Me NH2 1Me-5-1HIdz C 451 (M⁺ + 1) N-h-232NA N-h-231 2,3DFBn H H NH2 1Me-5-1HIdz C 437 (M⁺ + 1) N-h-233 ND1 N-h-513,4DFBn H Me NH2 5-Ind C 436 (M⁺ + 1) N-h-234 NA N-h-233 3,4DFBn H H NH25-Ind C 422 (M⁺ + 1) N-h-235 ND1 N-h-53 3,4DFBn H Me NH2 1Me-5-Ind C 450(M⁺ + 1) N-h-236 NA N-h-235 3,4DFBn H H NH2 1Me-5-Ind C 436 (M⁺ + 1)N-h-237 ND1 N-h-55 3,4DFBn H Me NH2 1Me-5-1HIdz C 451 (M⁺ + 1) N-h-238NA N-h-237 3,4DFBn H H NH2 1Me-5-1HIdz C 437 (M⁺ + 1) N-h-239 ND1 N-h-574PhBn H Me NH2 2-Nap C 487 (M⁺ + 1) N-h-240 NA N-h-239 4PhBn H H NH22-Nap C 473 (M⁺ + 1) N-h-241 ND1 N-h-59 4PhBn H Me NH2 5-Ind C 476(M⁺ + 1) N-h-242 NA N-h-241 4PhBn H H NH2 5-Ind C 462 (M⁺ + 1) N-h-243ND1 N-h-61 4PhBn H Me NH2 1Me-5-Ind C 490 (M⁺ + 1) N-h-244 NA N-h-2434PhBn H H NH2 1Me-5-Ind C 476 (M⁺ + 1) N-h-245 ND1 N-h-63 4PhBn H Me NH25-1HIdz C 477 (M⁺ + 1) N-h-246 NA N-h-245 4PhBn H H NH2 5-1HIdz C 463(M⁺ + 1) N-h-247 ND1 N-h-65 2CF3Bn H Me NH2 2-Nap C 479 (M⁺ + 1) N-h-248NA N-h-247 2CF3Bn H H NH2 2-Nap C 465 (M⁺ + 1) N-h-249 ND1 N-h-67 2CF3BnH Me NH2 5-Ind C 468 (M⁺ + 1) N-h-250 NA N-h-249 2CF3Bn H H NH2 5-Ind C454 (M⁺ + 1) N-h-251 ND1 N-h-69 2CF3Bn H Me NH2 1Me-5-Ind C 482 (M⁺ + 1)N-h-252 NA N-h-251 2CF3Bn H H NH2 1Me-5-Ind C 468 (M⁺ + 1) N-h-253 ND1N-h-71 2CF3Bn H Me NH2 5-1HIdz C 469 (M⁺ + 1) N-h-254 NA N-h-253 2CF3BnH H NH2 5-1HIdz C 455 (M⁺ + 1) N-h-255 ND1 N-h-73 2-TF H Me NH2 5-Ind C406 (M⁺ + 1) N-h-256 NA N-h-255 2-TF H H NH2 5-Ind C 392 (M⁺ + 1)N-h-257 ND1 N-h-75 2-TF H Me NH2 1Me-5-Ind C 420 (M⁺ + 1) N-h-258 NAN-h-257 2-TF H H NH2 1Me-5-Ind C 406 (M⁺ + 1) N-h-259 ND1 N-h-77 2-TF HMe NH2 1Me-5-1HIdz C 421 (M⁺ + 1) N-h-260 NA N-h-259 2-TF H H NH21Me-5-1HIdz C 407 (M⁺ + 1) N-h-261 ND1 N-h-79 3-TF H Me NH2 5-Ind C 406(M⁺ + 1) N-h-262 NA N-h-261 3-TF H H NH2 5-Ind C 392 (M⁺ + 1) N-h-263ND1 N-h-81 3-TF H Me NH2 1Me-5-Ind C 420 (M⁺ + 1) N-h-264 NA N-h-2633-TF H H NH2 1Me-5-Ind C 406 (M⁺ + 1) N-h-265 ND1 N-h-83 3-TF H Me NH25-1HIdz C 407 (M⁺ + 1) N-h-266 NA N-h-265 3-TF H H NH2 5-1HIdz C 393(M⁺ + 1) N-h-267 ND1 N-h-85 3-TF H Me NH2 1Me-5-1HIdz C 421 (M⁺ + 1)N-h-268 NA N-h-267 3-TF H H NH2 1Me-5-1HIdz C 407 (M⁺ + 1) N-h-269 ND1N-h-87 2-FR H Me NH2 2Nap C 401 (M⁺ + 1) N-h-270 NA N-h-269 2-FR H H NH22Nap C 387 (M⁺ + 1) N-h-271 ND1 N-h-89 2-FR H Me NH2 5-Ind C 390(M⁺ + 1) N-h-272 NA N-h-271 2-FR H H NH2 5-Ind C 376 (M⁺ + 1) N-h-273ND1 N-h-91 2-FR H Me NH2 1Me-5-1HIdz C 405 (M⁺ + 1) N-h-274 NA N-h-2732-FR H H NH2 1Me-5-1HIdz C 391 (M⁺ + 1)

TABLE N-H-7 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-h-275 ND1 N-h-93 Bn Me Me NH2 2-Nap C 425 (M⁺ + 1) N-h-276 NA N-h-275Bn Me H NH2 2-Nap C 411 (M⁺ + 1) N-h-277 ND1 N-h-95 Bn Me Me NH2 5-Ind C414 (M⁺ + 1) N-h-278 NA N-h-277 Bn Me H NH2 5-Ind C 400 (M⁺ + 1) N-h-279ND1 N-h-97 Bn Me Me NH2 1Me-5-Ind C 428 (M⁺ + 1) N-h-280 NA N-h-279 BnMe H NH2 1Me-5-Ind C 414 (M⁺ + 1) N-h-281 ND1 N-h-99 Bn Me Me NH25-1HIdz C 415 (M⁺ + 1) N-h-282 NA N-h-281 Bn Me H NH2 5-1HIdz C 401(M⁺ + 1) N-h-283 ND1 N-h-101 Bn Me Me NH2 1Me-5-IHIdz C 429 (M⁺ + 1)N-h-284 NA N-h-283 Bn Me H NH2 1Me-5-1HIdz C 415 (M⁺ + 1) N-h-285 ND1N-h-103 Bn Me Me NH2 3-Qu C 426 (M⁺ + 1) N-h-286 NA N-h-285 Bn Me H NH23-Qu C 412 (M⁺ + 1) N-h-287 ND1 N-h-105 Bn Me Me NH2 6-Qu C 426 (M⁺ + 1)N-h-288 NA N-h-287 Bn Me H NH2 6-Qu C 412 (M⁺ + 1) N-h-289 ND1 N-h-107Bn Me Me NH2 6-IQ C 426 (M⁺ + 1) N-h-290 NA N-h-289 Bn Me H NH2 6-IQ C412 (M⁺ + 1) N-h-291 ND1 N-h-109 4FBn Me Me NH2 2-Nap C 443 (M⁺ + 1)N-h-292 NA N-h-291 4FBn Me H NH2 2-Nap C 429 (M⁺ + 1) N-h-293 ND1N-h-111 4FBn Me Me NH2 5-Ind C 432 (M⁺ + 1) N-h-294 NA N-h-293 4FBn Me HNH2 5-Ind C 418 (M⁺ + 1) N-h-295 ND1 N-h-113 4FBn Me Me NH2 1Me-5-Ind C446 (M⁺ + 1) N-h-296 NA N-h-295 4FBn Me H NH2 1Me-5-Ind C 432 (M⁺ + 1)N-h-297 ND1 N-h-115 4FBn Me Me NH2 5-1HIdz C 433 (M⁺ + 1) N-h-298 NAN-h-297 4FBn Me H NH2 5-1HIdz C 419 (M⁺ + 1) N-h-299 ND1 N-h-117 4FBn MeMe NH2 1Me-5-1HIdz C 447 (M⁺ + 1) N-h-300 NA N-h-299 4FBn Me H NH21Me-5-1HIdz C 433 (M⁺ + 1) N-h-301 ND1 N-h-119 2FBn Me Me NH2 2-Nap C443 (M⁺ + 1) N-h-302 NA N-h-301 2FBn Me H NH2 2-Nap C 429 (M⁺ + 1)N-h-303 ND1 N-h-121 2FBn Me Me NH2 1Me-5-Ind C 446 (M⁺ + 1) N-h-304 NAN-h-303 2FBn Me H NH2 1Me-5-Ind C 432 (M⁺ + 1) N-h-305 ND1 N-h-123 2FBnMe Me NH2 5-1HIdz C 433 (M⁺ + 1) N-h-306 NA N-h-305 2FBn Me H NH25-1HIdz C 419 (M⁺ + 1) N-h-307 ND1 N-h-125 2FBn Me Me NH2 1Me-5-1HIdz C447 (M⁺ + 1) N-h-308 NA N-h-307 2FBn Me H NH2 1Me-5-1HIdz C 433 (M⁺ + 1)N-h-309 ND1 N-h-127 3FBn Me Me NH2 2-Nap C 443 (M⁺ + 1) N-h-310 NAN-h-309 3FBn Me H NH2 2-Nap C 429 (M⁺ + 1) N-h-311 ND1 N-h-129 3FBn MeMe NH2 1Me-5-Ind C 446 (M⁺ + 1) N-h-312 NA N-h-311 3FBn Me H NH21Me-5-Ind C 432 (M⁺ + 1) N-h-313 ND1 N-h-131 3FBn Me Me NH2 5-1HIdz C433 (M⁺ + 1) N-h-314 NA N-h-313 3FBn Me H NH2 5-1HIdz C 419 (M⁺ + 1)N-h-315 ND1 N-h-133 3FBn Me Me NH2 1Me-5-1HIdz C 447 (M⁺ + 1) N-h-316 NAN-h-315 3FBn Me H NH2 1Me-5-1HIdz C 433 (M⁺ + 1) N-h-317 ND1 N-h-1352,3DFBn Me Me NH2 2-Nap C 461 (M⁺ + 1) N-h-318 NA N-h-317 2,3DFBn Me HNH2 2-Nap C 447 (M⁺ + 1) N-h-319 ND1 N-h-137 2,3DFBn Me Me NH2 1Me-5-IndC 464 (M⁺ + 1) N-h-320 NA N-h-319 2,3DFBn Me H NH2 1Me-5-Ind C 450 (M⁺ +1)

TABLE N-H-8 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-h-321 ND1 N-h-139 2,3DFBn Me Me NH2 5-1HIdz C 451 (M⁺ + 1) N-h-322 NAN-h-321 2,3DFBn Me H NH2 5-1HIdz C 437 (M⁺ + 1) N-h-323 ND1 N-h-1412,3DFBn Me Me NH2 1Me-5-1HIdz C 465 (M⁺ + 1) N-h-324 NA N-h-323 2,3DFBnMe H NH2 1Me-5-1HIdz C 451 (M⁺ + 1) N-h-325 ND1 N-h-143 3,4DFBn Me MeNH2 2-Nap C 461 (M⁺ + 1) N-h-326 NA N-h-325 3,4DFBn Me H NH2 2-Nap C 447(M⁺ + 1) N-h-327 ND1 N-h-145 3,4DFBn Me Me NH2 1Me-5-Ind C 464 (M⁺ + 1)N-h-328 NA N-h-327 3,4DFBn Me H NH2 1Me-5-Ind C 450 (M⁺ + 1) N-h-329 ND1N-h-147 3,4DFBn Me Me NH2 1Me-5-1HIdz C 465 (M⁺ + 1) N-h-330 NA N-h-3293,4DFBn Me H NH2 1Me-5-1HIdz C 451 (M⁺ + 1) N-h-331 ND1 N-h-149 4PhBn MeMe NH2 2-Nap C 501 (M⁺ + 1) N-h-332 NA N-h-331 4PhBn Me H NH2 2-Nap C487 (M⁺ + 1) N-h-333 ND1 N-h-151 4PhBn Me Me NH2 5-Ind C 490 (M⁺ + 1)N-h-334 NA N-h-333 4PhBn Me H NH2 5-Ind C 476 (M⁺ + 1) N-h-335 ND1N-h-153 4PhBn Me Me NH2 1Me-5-Ind C 504 (M⁺ + 1) N-h-336 NA N-h-3354PhBn Me H NH2 1Me-5-Ind C 490 (M⁺ + 1) N-h-337 ND1 N-h-155 4PhBn Me MeNH2 1Me-5-1HIdz C 505 (M⁺ + 1) N-h-338 NA N-h-337 4PhBn Me H NH21Me-5-1HIdz C 491 (M⁺ + 1) N-h-339 ND1 N-h-157 2CF3Bn Me Me NH2 2-Nap C493 (M⁺ + 1) N-h-340 NA N-h-339 2CF3Bn Me H NH2 2-Nap C 479 (M⁺ + 1)N-h-341 ND1 N-h-159 2CF3Bn Me Me NH2 5-Ind C 482 (M⁺ + 1) N-h-342 NAN-h-341 2CF3Bn Me H NH2 5-Ind C 468 (M⁺ + 1) N-h-343 ND1 N-h-161 2CF3BnMe Me NH2 1Me-5-Ind C 496 (M⁺ + 1) N-h-344 NA N-h-343 2CF3Bn Me H NH21Me-5-Ind C 482 (M⁺ + 1) N-h-345 ND1 N-h-163 2CF3Bn Me Me NH2 5-1HIdz C483 (M⁺ + 1) N-h-346 NA N-h-345 2CF3Bn Me H NH2 5-1HIdz C 469 (M⁺ + 1)N-h-347 ND1 N-h-165 2-TF Me Me NH2 2-Nap C 431 (M⁺ + 1) N-h-348 NAN-h-347 2-TF Me H NH2 2-Nap C 417 (M⁺ + 1) N-h-349 ND1 N-h-167 2-TF MeMe NH2 1Me-5-Ind C 434 (M⁺ + 1) N-h-350 NA N-h-349 2-TF Me H NH21Me-5-Ind C 420 (M⁺ + 1) N-h-351 ND1 N-h-169 2-TF Me Me NH2 1Me-5-1HIdzC 435 (M⁺ + 1) N-h-352 NA N-h-351 2-TF Me H NH2 1Me-5-1HIdz C 421(M⁺ + 1) N-h-353 ND1 N-h-171 3-TF Me Me NH2 2-Nap C 431 (M⁺ + 1) N-h-354NA N-h-353 3-TF Me H NH2 2-Nap C 417 (M⁺ + 1) N-h-355 ND1 N-h-173 3-TFMe Me NH2 5-Ind C 420 (M⁺ + 1) N-h-356 NA N-h-355 3-TF Me H NH2 5-Ind C406 (M⁺ + 1) N-h-357 ND1 N-h-175 3-TF Me Me NH2 1Me-5-Ind C 434 (M⁺ + 1)N-h-358 NA N-h-357 3-TF Me H NH2 1Me-5-Ind C 420 (M⁺ + 1) N-h-359 ND1N-h-177 3-TF Me Me NH2 1Me-5-1HIdz C 435 (M⁺ + 1) N-h-360 NA N-h-3593-TF Me H NH2 1Me-5-1HIdz C 421 (M⁺ + 1) N-h-361 ND1 N-h-179 2-FR Me MeNH2 2-Nap C 415 (M⁺ + 1) N-h-362 NA N-h-361 2-FR Me H NH2 2-Nap C 401(M⁺ + 1) N-h-363 ND1 N-h-181 2-FR Me Me NH2 5-Ind C 404 (M⁺ + 1) N-h-364NA N-h-363 2-FR Me H NH2 5-Ind C 390 (M⁺ + 1) N-h-365 ND1 N-h-183 2-FRMe Me NH2 1Me-5-1HIdz C 419 (M⁺ + 1) N-h-366 NA N-h-365 2-FR Me H NH21Me-5-1HIdz C 405 (M⁺ + 1)

TABLE N-H-9 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-h-367 NN1 N-h-275 CH₃I Bn Me Me NHMe 2-Nap C 439 (M⁺ + 1) N-h-368 NAN-h-367 Bn Me H NHMe 2-Nap C 425 (M⁺ + 1) N-h-369 NN1 N-h-279 CH₃I Bn MeMe NHMe 1Me-5-Ind C 442 (M⁺ + 1) N-h-370 NA N-h-369 Bn Me H NHMe1Me-5-Ind C 428 (M⁺ + 1) N-h-371 NN1 N-h-283 CH₃I Bn Me Me NHMe1Me-5-1HIdz C 443 (M⁺ + 1) N-h-372 NA N-h-371 Bn Me H NHMe 1Me-5-1HIdz C429 (M⁺ + 1) N-h-373 NN1 N-h-285 CH₃I Bn Me Me NHMe 3-Qu C 440 (M⁺ + 1)N-h-374 NA N-h-373 Bn Me H NHMe 3-Qu C 426 (M⁺ + 1) N-h-375 NN1 N-h-289CH₃I Bn Me Me NHMe 6-IQ C 440 (M⁺ + 1) N-h-376 NA N-h-375 Bn Me H NHMe6-IQ C 426 (M⁺ + 1) N-h-377 NN1 N-h-291 CH₃I 4FBn Me Me NHMe 2-Nap C 457(M⁺ + 1) N-h-378 NA N-h-377 4FBn Me H NHMe 2-Nap C 443 (M⁺ + 1) N-h-379NN1 N-h-295 CH₃I 4FBn Me Me NHMe 1Me-5-Ind C 460 (M⁺ + 1) N-h-380 NAN-h-379 4FBn Me H NHMe 1Me-5-Ind C 446 (M⁺ + 1) N-h-381 NN1 N-h-299 CH₃I4FBn Me Me NHMe 1Me-5-1HIdz C 461 (M⁺ + 1) N-h-382 NA N-h-381 4FBn Me HNHMe 1Me-5-1HIdz C 447 (M⁺ + 1) N-h-383 NN1 N-h-301 CH₃I 2FBn Me Me NHMe2-Nap C 457 (M⁺ + 1) N-h-384 NA N-h-383 2FBn Me H NHMe 2-Nap C 443(M⁺ + 1) N-h-385 NN1 N-h-303 CH₃I 2FBn Me Me NHMe 1Me-5-Ind C 460(M⁺ + 1) N-h-386 NA N-h-385 2FBn Me H NHMe 1Me-5-Ind C 446 (M⁺ + 1)N-h-387 NN1 N-h-307 CH₃I 2FBn Me Me NHMe 1Me-5-1HIdz C 461 (M⁺ + 1)N-h-388 NA N-h-387 2FBn Me H NHMe 1Me-5-1HIdz C 447 (M⁺ + 1) N-h-389 NN1N-h-309 CH₃I 3FBn Me Me NHMe 2-Nap C 457 (M⁺ + 1) N-h-390 NA N-h-3893FBn Me H NHMe 2-Nap C 443 (M⁺ + 1) N-h-391 NN1 N-h-311 CH₃I 3FBn Me MeNHMe 1Me-5-Ind C 460 (M⁺ + 1) N-h-392 NA N-h-391 3FBn Me H NHMe1Me-5-Ind C 446 (M⁺ + 1) N-h-393 NN1 N-h-317 CH₃I 2,3DFBn Me Me NHMe2-Nap C 475 (M⁺ + 1) N-h-394 NA N-h-393 2,3DFBn Me H NHMe 2-Nap C 461(M⁺ + 1) N-h-395 NN1 N-h-323 CH₃I 2,3DFBn Me Me NHMe 1Me-5-1HIdz C 479(M⁺ + 1) N-h-396 NA N-h-395 2,3DFBn Me H NHMe 1Me-5-1HIdz C 465 (M⁺ + 1)N-h-397 NN1 N-h-327 CH₃I 3,4DFBn Me Me NHMe 1Me-5-Ind C 478 (M⁺ + 1)N-h-398 NA N-h-397 3,4DFBn Me H NHMe 1Me-5-Ind C 464 (M⁺ + 1) N-h-399NN1 N-h-331 CH₃I 4PhBn Me Me NHMe 2-Nap C 515 (M⁺ + 1) N-h-400 NAN-h-399 4PhBn Me H NHMe 2-Nap C 501 (M⁺ + 1) N-h-401 NN1 N-h-337 CH₃I4PhBn Me Me NHMe 1Me-5-1HIdz C 519 (M⁺ + 1) N-h-402 NA N-h-401 4PhBn MeH NHMe 1Me-5-1HIdz C 505 (M⁺ + 1) N-h-403 NN1 N-h-339 CH₃I 2CF3Bn Me MeNHMe 2-Nap C 507 (M⁺ + 1) N-h-404 NA N-h-403 2CF3Bn Me H NHMe 2-Nap C493 (M⁺ + 1) N-h-405 NN1 N-h-343 CH₃I 2CF3Bn Me Me NHMe 1Me-5-Ind C 510(M⁺ + 1) N-h-406 NA N-h-405 2CF3Bn Me H NHMe 1Me-5-Ind C 496 (M⁺ + 1)N-h-407 NN1 N-h-347 CH₃I 2-TF Me Me NHMe 2-Nap C 445 (M⁺ + 1) N-h-408 NAN-h-407 2-TF Me H NHMe 2-Nap C 431 (M⁺ + 1) N-h-409 NN1 N-h-357 CH₃I3-TF Me Me NHMe 1Me-5-Ind C 448 (M⁺ + 1) N-h-410 NA N-h-409 3-TF Me HNHMe 1Me-5-Ind C 434 (M⁺ + 1) N-h-411 NN1 N-h-365 CH₃I 2-FR Me Me NHMe1Me-5-1HIdz C 433 (M⁺ + 1) N-h-412 NA N-h-411 2-FR Me H NHMe 1Me-5-1HIdzC 419 (M⁺ + 1)

TABLE N-H-10 LCMS Exp. Syn SM1 SM2 Rz Ry Y Zx AR method RTime MassN-h-413 NN2 N-h-275 CH₃I Bn Me Me NMe2 2-Nap C 453 (M⁺ + 1) N-h-414 NAN-h-413 Bn Me H NMe2 2-Nap C 439 (M⁺ + 1) N-h-415 NN2 N-h-279 CH₃I Bn MeMe NMe2 1Me-5-Ind C 456 (M⁺ + 1) N-h-416 NA N-h-415 Bn Me H NMe21Me-5-Ind C 442 (M⁺ + 1) N-h-417 NN2 N-h-283 CH₃I Bn Me Me NMe21Me-5-1HIdz C 457 (M⁺ + 1) N-h-418 NA N-h-417 Bn Me H NMe2 1Me-5-1HIdz C443 (M⁺ + 1) N-h-419 NN2 N-h-285 CH₃I Bn Me Me NMe2 3-Qu C 454 (M⁺ + 1)N-h-420 NA N-h-419 Bn Me H NMe2 3-Qu C 440 (M⁺ + 1) N-h-421 NN2 N-h-289CH₃I Bn Me Me NMe2 6-IQ C 454 (M⁺ + 1) N-h-422 NA N-h-421 Bn Me H NMe26-IQ C 440 (M⁺ + 1) N-h-423 NN2 N-h-291 CH₃I 4FBn Me Me NMe2 2-Nap C 471(M⁺ + 1) N-h-424 NA N-h-423 4FBn Me H NMe2 2-Nap C 457 (M⁺ + 1) N-h-425NN2 N-h-295 CH₃I 4FBn Me Me NMe2 1Me-5-Ind C 474 (M⁺ + 1) N-h-426 NAN-h-425 4FBn Me H NMe2 1Me-5-Ind C 460 (M⁺ + 1) N-h-427 NN2 N-h-299 CH₃I4FBn Me Me NMe2 1Me-5-1HIdz C 475 (M⁺ + 1) N-h-428 NA N-h-427 4FBn Me HNMe2 1Me-5-1HIdz C 461 (M⁺ + 1) N-h-429 NN2 N-h-301 CH₃I 2FBn Me Me NMe22-Nap C 471 (M⁺ + 1) N-h-430 NA N-h-429 2FBn Me H NMe2 2-Nap C 457(M⁺ + 1) N-h-431 NN2 N-h-303 CH₃I 2FBn Me Me NMe2 1Me-5-Ind C 474(M⁺ + 1) N-h-432 NA N-h-431 2FBn Me H NMe2 1Me-5-Ind C 460 (M⁺ + 1)N-h-433 NN2 N-h-307 CH₃I 2FBn Me Me NMe2 1Me-5-1HIdz C 475 (M⁺ + 1)N-h-434 NA N-h-433 2FBn Me H NMe2 1Me-5-1HIdz C 461 (M⁺ + 1) N-h-435 NN2N-h-309 CH₃I 3FBn Me Me NMe2 2-Nap C 471 (M⁺ + 1) N-h-436 NA N-h-4353FBn Me H NMe2 2-Nap C 457 (M⁺ + 1) N-h-437 NN2 N-h-311 CH₃I 3FBn Me MeNMe2 1Me-5-Ind C 474 (M⁺ + 1) N-h-438 NA N-h-437 3FBn Me H NMe21Me-5-Ind C 460 (M⁺ + 1) N-h-439 NN2 N-h-317 CH₃I 2,3DFBn Me Me NMe22-Nap C 489 (M⁺ + 1) N-h-440 NA N-h-439 2,3DFBn Me H NMe2 2-Nap C 475(M⁺ + 1) N-h-441 NN2 N-h-323 CH₃I 2,3DFBn Me Me NMe2 1Me-5-1HIdz C 493(M⁺ + 1) N-h-442 NA N-h-441 2,3DFBn Me H NMe2 1Me-5-1HIdz C 479 (M⁺ + 1)N-h-443 NN2 N-h-327 CH₃I 3,4DFBn Me Me NMe2 1Me-5-Ind C 492 (M⁺ + 1)N-h-444 NA N-h-443 3,4DFBn Me H NMe2 1Me-5-Ind C 478 (M⁺ + 1) N-h-445NN2 N-h-331 CH₃I 4PhBn Me Me NMe2 2-Nap C 529 (M⁺ + 1) N-h-446 NAN-h-445 4PhBn Me H NMe2 2-Nap C 515 (M⁺ + 1) N-h-447 NN2 N-h-337 CH₃I4PhBn Me Me NMe2 1Me-5-1HIdz C 533 (M⁺ + 1) N-h-448 NA N-h-447 4PhBn MeH NMe2 1Me-5-1HIdz C 519 (M⁺ + 1) N-h-449 NN2 N-h-339 CH₃I 2CF3Bn Me MeNMe2 2-Nap C 521 (M⁺ + 1) N-h-450 NA N-h-449 2CF3Bn Me H NMe2 2-Nap C507 (M⁺ + 1) N-h-451 NN2 N-h-343 CH₃I 2CF3Bn Me Me NMe2 1Me-5-Ind C 524(M⁺ + 1) N-h-452 NA N-h-451 2CF3Bn Me H NMe2 1Me-5-Ind C 510 (M⁺ + 1)N-h-453 NN2 N-h-347 CH₃I 2-TF Me Me NMe2 2-Nap C 459 (M⁺ + 1) N-h-454 NAN-h-453 2-TF Me H NMe2 2-Nap C 445 (M⁺ + 1) N-h-455 NN2 N-h-357 CH₃I3-TF Me Me NMe2 1Me-5-Ind C 462 (M⁺ + 1) N-h-456 NA N-h-455 3-TF Me HNMe2 1Me-5-Ind C 448 (M⁺ + 1) N-h-457 NN2 N-h-365 CH₃I 2-FR Me Me NMe21Me-5-1HIdz C 447 (M⁺ + 1) N-h-458 NA N-h-457 2-FR Me H NMe2 1Me-5-1HIdzC 433 (M⁺ + 1)

Examples N-I-1 to N-I-138

Typical examples of the compounds of the present invention that can beobtained by reacting and treating corresponding starting compounds usingany of the methods described in the present specification are shown inTable-N-I-1 to Table-N-I-8. In the tables, the compound numbers arementioned in the columns indicated as “Exp.”. In the tables, usedmethods among the aforementioned synthesis methods are shown in thecolumns of “Syn” with symbols, the starting compounds 1 are mentioned inthe columns of “SM1”, and the starting compounds 2 are mentioned in thecolumns of “SM2”.

TABLE-N-I-1

LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-i-1 NB1Int.n-111 BRA1

Me NO2 2-Nap C 405 (M⁺ + 1) N-i-2 NA N-i-1

H NO2 2-Nap C 391 (M⁺ + 1) N-i-3 NB1 Int.n-111 BRA2

Me NO2 5-1Ind C 394 (M⁺ + 1) N-i-4 NA N-i-3

H NO2 5-1Ind C 380 (M⁺ + 1) N-i-5 NB1 Int.n-111 BRA3

Me NO2 1Me-5-Ind C 408 (M⁺ + 1) N-i-6 NA N-i-5

H NO2 1Me-5-Ind C 394 (M⁺ + 1) N-i-7 NB1 Int.n-111 BRA5

Me NO2 5-1HIdz C 395 (M⁺ + 1) N-i-8 NA N-i-7

H NO2 5-1HIdz C 381 (M⁺ + 1) N-i-9 NB1 Int.n-111 BRA6

Me NO2 1Me-5-1HIdz C 409 (M⁺ + 1) N-i-10 NA N-i-9

H NO2 1Me-5-1HIdz C 395 (M⁺ + 1) N-i-11 NB1 Int.n-111 BRA9

Me NO2 5-Bzt C 412 (M⁺ + 1) N-i-12 NA N-i-11

H NO2 5-Bzt C 398 (M⁺ + 1) N-i-13 NB1 Int.n-111 BRA 10

Me NO2 3-Qu C 406 (M⁺ + 1) N-i-14 NA N-i-13

H NO2 3-Qu C 392 (M⁺ + 1) N-i-15 NB1 Int.n-111 BRA 11

Me NO2 6-Qu C 406 (M⁺ + 1) N-i-16 NA N-i-15

H NO2 6-Qu C 392 (M⁺ + 1) N-i-17 NB1 Int.n-112 BRA1

Me NO2 2-Nap C 421 (M⁺ + 1) N-i-18 NA N-i-17

H NO2 2-Nap C 407 (M⁺ + 1) N-i-19 NB1 Int.n-112 BRA2

Me NO2 5-1Ind C 410 (M⁺ + 1) N-i-20 NA N-i-19

H NO2 5-1Ind C 396 (M⁺ + 1) N-i-21 NB1 Int.n-112 BRA3

Me NO2 1Me-5-Ind C 424 (M⁺ + 1) N-i-22 NA N-i-21

H NO2 1Me-5-Ind C 410 (M⁺ + 1)

TABLE-N-I-2 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-i-23NB1 Int.n-112 BRA5

Me NO2 5-1HIdz C 411 (M⁺ + 1) N-i-24 NA N-i-23

H NO2 5-1HIdz C 397 (M⁺ + 1) N-i-25 NB1 Int.n-112 BRA6

Me NO2 1Me-5-1HIdz C 425 (M⁺ + 1) N-i-26 NA N-i-25

H NO2 1Me-5-1HIdz C 411 (M⁺ + 1) N-i-27 NB1 Int.n-113 BRA1

Me NO2 2-Nap C 419 (M⁺ + 1) N-i-28 NA N-i-27

H NO2 2-Nap C 405 (M⁺ + 1) N-i-29 NB1 Int.n-113 BRA2

Me NO2 5-1Ind C 408 (M⁺ + 1) N-i-30 NA N-i-29

H NO2 5-1Ind C 394 (M⁺ + 1) N-i-31 NB1 Int.n-113 BRA3

Me NO2 1Me-5-Ind C 422 (M⁺ + 1) N-i-32 NA N-i-31

H NO2 1Me-5-Ind C 408 (M⁺ + 1) N-i-33 NB1 Int.n-113 BRA5

Me NO2 5-1HIdz C 409 (M⁺ + 1) N-i-34 NA N-i-33

H NO2 5-1HIdz C 395 (M⁺ + 1) N-i-35 NB1 Int.n-113 BRA6

Me NO2 1Me-5-1HIdz C 423 (M⁺ + 1) N-i-36 NA N-i-35

H NO2 1Me-5-1HIdz C 409 (M⁺ + 1) N-i-37 NB1 Int.n-113 BRA11

Me NO2 6-Qu C 420 (M⁺ + 1) N-i-38 NA N-i-37

H NO2 6-Qu C 406 (M⁺ + 1) N-i-39 NB1 Int.n-114 BRA1

Me NO2 2-Nap C 433 (M⁺ + 1) N-i-40 NA N-i-39

H NO2 2-Nap C 419 (M⁺ + 1) N-i-41 NB1 Int.n-114 BRA3

Me NO2 1Me-5-Ind C 437 (M⁺ + 1) N-i-42 NA N-i-41

H NO2 1Me-5-Ind C 423 (M⁺ + 1) N-i-43 NB1 Int.n-114 BRA5

Me NO2 5-1HIdz C 423 (M⁺ + 1) N-i-44 NA N-i-43

H NO2 5-1HIdz C 409 (M⁺ + 1)

TABLE-N-I-3 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-i-45NB1 Int.n-114 BRA6

Me NO2 1Me-5-1HIdz C 437 (M⁺ + 1) N-i-46 NA N-i-45

H NO2 1Me-5-1HIdz C 423 (M⁺ + 1) N-i-47 NB1 Int.n-115 BRA3

Me NO2 1Me-5-Ind C 436 (M⁺ + 1) N-i-48 NA N-i-47

H NO2 1Me-5-Ind C 422 (M⁺ + 1) N-i-49 NB1 Int.n-115 BRA5

Me NO2 5-1HIdz C 423 (M⁺ + 1) N-i-50 NA N-i-49

H NO2 5-1HIdz C 409 (M⁺ + 1) N-i-51 NB1 Int.n-115 BRA6

Me NO2 1Me-5-1HIdz C 437 (M⁺ + 1) N-i-52 NA N-i-51

H NO2 1Me-5-1HIdz C 423 (M⁺ + 1) N-i-53 ND1 N-i-1

Me NH2 2-Nap C 375 (M⁺ + 1) N-i-54 NA N-i-53

H NH2 2-Nap C 361 (M⁺ + 1) N-i-55 ND1 N-i-3

Me NH2 5-1Ind C 364 (M⁺ + 1) N-i-56 NA N-i-55

H NH2 5-1Ind C 350 (M⁺ + 1) N-i-57 ND1 N-i-5

Me NH2 1Me-5-Ind C 378 (M⁺ + 1) N-i-58 NA N-i-57

H NH2 1Me-5-Ind C 364 (M⁺ + 1) N-i-59 ND1 N-i-7

Me NH2 5-1HIdz C 365 (M⁺ + 1) N-i-60 NA N-i-59

H NH2 5-1HIdz C 351 (M⁺ + 1) N-i-61 ND1 N-i-9

Me NH2 1Me-5-1HIdz C 379 (M⁺ + 1) N-i-62 NA N-i-61

H NH2 1Me-5-1HIdz C 365 (M⁺ + 1) N-i-63 ND1 N-i-11

Me NH2 5-Bzt C 382 (M⁺ + 1) N-i-64 NA N-i-63

H NH2 5-Bzt C 368 (M⁺ + 1) N-i-65 ND1 N-i-13

Me NH2 3-Qu C 376 (M⁺ + 1) N-i-66 NA N-i-65

H NH2 3-Qu C 362 (M⁺ + 1)

TABLE-N-I-4 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-i-67ND1 N-i-15

Me NH2 6-Qu C 376 (M⁺ + 1) N-i-68 NA N-i-67

H NH2 6-Qu C 362 (M⁺ + 1) N-i-69 ND1 N-i-17

Me NH2 2-Nap C 391 (M⁺ + 1) N-i-70 NA N-i-69

H NH2 2-Nap C 377 (M⁺ + 1) N-i-71 ND1 N-i-19

Me NH2 5-1Ind C 380 (M⁺ + 1) N-i-72 NA N-i-71

H NH2 5-1Ind C 366 (M⁺ + 1) N-i-73 ND1 N-i-21

Me NH2 1Me-5-Ind C 394 (M⁺ + 1) N-i-74 NA N-i-73

H NH2 1Me-5-Ind C 380 (M⁺ + 1) N-i-75 ND1 N-i-23

Me NH2 5-1HIdz C 381 (M⁺ + 1) N-i-76 NA N-i-75

H NH2 5-1HIdz C 367 (M⁺ + 1) N-i-77 ND1 N-i-25

Me NH2 1Me-5-1HIdz C 395 (M⁺ + 1) N-i-78 NA N-i-77

H NH2 1Me-5-1HIdz C 381 (M⁺ + 1) N-i-79 ND1 N-i-27

Me NH2 2-Nap C 389 (M⁺ + 1) N-i-80 NA N-i-79

H NH2 2-Nap C 375 (M⁺ + 1) N-i-81 ND1 N-i-29

Me NH2 5-1Ind C 378 (M⁺ + 1) N-i-82 NA N-i-81

H NH2 5-1Ind C 364 (M⁺ + 1) N-i-83 ND1 N-i-31

Me NH2 1Me-5-Ind C 392 (M⁺ + 1) N-i-84 NA N-i-83

H NH2 1Me-5-Ind C 378 (M⁺ + 1) N-i-85 ND1 N-i-33

Me NH2 5-1HIdz C 379 (M⁺ + 1) N-i-86 NA N-i-85

H NH2 5-1HIdz C 365 (M⁺ + 1) N-i-87 ND1 N-i-35

Me NH2 1Me-5-1HIdz C 393 (M⁺ + 1) N-i-88 NA N-i-87

H NH2 1Me-5-1HIdz C 379 (M⁺ + 1)

TABLE-N-I-5 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime Mass N-i-89ND1 N-i-37

Me NH2 6-Qu C 390 (M⁺ + 1) N-i-90 NA N-i-89

H NH2 6-Qu C 376 (M⁺ + 1) N-i-91 ND1 N-i-39

Me NH2 2-Nap C 403 (M⁺ + 1) N-i-92 NA N-i-91

H NH2 2-Nap C 389 (M⁺ + 1) N-i-93 ND1 N-i-41

Me NH2 1Me-5-Ind C 406 (M⁺ + 1) N-i-94 NA N-i-93

H NH2 1Me-5-Ind C 392 (M⁺ + 1) N-i-95 ND1 N-i-43

Me NH2 5-1Idz C 393 (M⁺ + 1) N-i-96 NA N-i-95

H NH2 5-1Idz C 379 (M⁺ + 1) N-i-97 ND1 N-i-45

Me NH2 1Me-5-1HIdz C 407 (M⁺ + 1) N-i-98 NA N-i-97

H NH2 1Me-5-1HIdz C 393 (M⁺ + 1) N-i-99 ND1 N-i-47

Me NH2 1Me-5-Ind C 406 (M⁺ + 1) N-i-100 NA N-i-99

H NH2 1Me-5-Ind C 392 (M⁺ + 1) N-i-101 ND1 N-i-49

Me NH2 5-1Idz C 393 (M⁺ + 1) N-i-102 NA N-i-101

H NH2 5-1Idz C 379 (M⁺ + 1) N-i-103 ND1 N-i-51

Me NH2 1Me-5-1HIdz C 407 (M⁺ + 1) N-i-104 NA N-i-103

H NH2 1Me-5-1HIdz C 393 (M⁺ + 1) N-i-105 NN1 N-i-53 CH₃I

Me NHMe 2-Nap C 389 (M⁺ + 1) N-i-106 NA N-i-105

H NHMe 2-Nap C 375 (M⁺ + 1) N-i-107 NN1 N-i-57 CH₃I

Me NHMe 1Me-5-Ind C 392 (M⁺ + 1) N-i-108 NA N-i-107

H NHMe 1Me-5-Ind C 378 (M⁺ + 1) N-i-109 NN1 N-i-61 CH₃I

Me NHMe 1Me-5-1HIdz C 393 (M⁺ + 1) N-i-110 NA N-i-109

H NHMe 1Me-5-1HIdz C 379 (M⁺ + 1)

TABLE-N-I-6 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime MassN-i-111 NN1 N-i-63 CH₃I

Me NHMe 5-Bzt C 396 (M⁺ + 1) N-i-112 NA N-i-111

H NHMe 5-Bzt C 382 (M⁺ + 1) N-i-113 NN1 N-i-65 CH₃I

Me NHMe 3-Qu C 390 (M⁺ + 1) N-i-114 NA N-i-113

H NHMe 3-Qu C 376 (M⁺ + 1) N-i-115 NN1 N-i-67 CH₃I

Me NHMe 6-Qu C 390 (M⁺ + 1) N-i-116 NA N-i-115

H NHMe 6-Qu C 376 (M⁺ + 1) N-i-117 NN1 N-i-69 CH₃I

Me NHMe 2-Nap C 405 (M⁺ + 1) N-i-118 NA N-i-117

H NHMe 2-Nap C 391 (M⁺ + 1) N-i-119 NN1 N-i-73 CH₃I

Me NHMe 1Me-5-Ind C 408 (M⁺ + 1) N-i-120 NA N-i-119

H NHMe 1Me-5-Ind C 394 (M⁺ + 1) N-i-121 NN1 N-i-77 CH₃I

Me NHMe 1Me-5-1HIdz C 409 (M⁺ + 1) N-i-122 NA N-i-121

H NHMe 1Me-5-1HIdz C 395 (M⁺ + 1) N-i-123 NN1 N-i-79 CH₃I

Me NHMe 2-Nap C 403 (M⁺ + 1) N-i-124 NA N-i-123

H NHMe 2-Nap C 389 (M⁺ + 1) N-i-125 NN1 N-i-83 CH₃I

Me NHMe 1Me-5-Ind C 406 (M⁺ + 1) N-i-126 NA N-i-125

H NHMe 1Me-5-Ind C 392 (M⁺ + 1) N-i-127 NN1 N-i-87 CH₃I

Me NHMe 1Me-5-1HIdz C 407 (M⁺ + 1) N-i-128 NA N-i-127

H NHMe 1Me-5-1HIdz C 393 (M⁺ + 1) N-i-129 NN1 N-i-91 CH₃I

Me NHMe 2-Nap C 417 (M⁺ + 1) N-i-130 NA N-i-129

H NHMe 2-Nap C 403 (M⁺ + 1) N-i-131 NN1 N-i-93 CH₃I

Me NHMe 1Me-5-Ind C 420 (M⁺ + 1) N-i-132 NA N-i-131

H NHMe 1Me-5-Ind C 406 (M⁺ + 1)

TABLE-N-I-7 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime MassN-i-133 NN1 N-i-97 CH₃I

Me NHMe 1Me-5-1HIdz C 421 (M⁺ + 1) N-i-134 NA N-i-133

H NHMe 1Me-5-1HIdz C 407 (M⁺ + 1) N-i-135 NN1 N-i-99 CH₃I

Me NHMe 1Me-5-Ind C 420 (M⁺ + 1) N-i-136 NA N-i-135

H NHMe 1Me-5-Ind C 406 (M⁺ + 1) N-i-137 NN1 N-i-103 CH₃I

Me NHMe 1Me-5-1HIdz C 421 (M⁺ + 1) N-i-138 NA N-i-137

H NHMe 1Me-5-1HIdz C 407 (M⁺ + 1) N-i-139 NN2 N-i-53 CH₃I

Me NMe2 2-Nap C 403 (M⁺ + 1) N-i-140 NA N-i-139

H NMe2 2-Nap C 389 (M⁺ + 1) N-i-141 NN2 N-i-57 CH₃I

Me NMe2 1Me-5-Ind C 406 (M⁺ + 1) N-i-142 NA N-i-141

H NMe2 1Me-5-Ind C 392 (M⁺ + 1) N-i-143 NN2 N-i-61 CH₃I

Me NMe2 1Me-5-1HIdz C 407 (M⁺ + 1) N-i-144 NA N-i-143

H NMe2 1Me-5-1HIdz C 393 (M⁺ + 1) N-i-145 NN2 N-i-63 CH₃I

Me NMe2 5-Bzt C 410 (M⁺ + 1) N-i-146 NA N-i-145

H NMe2 5-Bzt C 396 (M⁺ + 1) N-i-147 NN2 N-i-65 CH₃I

Me NMe2 3-Qu C 404 (M⁺ + 1) N-i-148 NA N-i-147

H NMe2 3-Qu C 390 (M⁺ + 1) N-i-149 NN2 N-i-67 CH₃I

Me NMe2 6-Qu C 404 (M⁺ + 1) N-i-150 NA N-i-149

H NMe2 6-Qu C 390 (M⁺ + 1) N-i-151 NN2 N-i-69 CH₃I

Me NMe2 2-Nap C 419 (M⁺ + 1) N-i-152 NA N-i-151

H NMe2 2-Nap C 405 (M⁺ + 1) N-i-153 NN2 N-i-73 CH₃I

Me NMe2 1Me-5-Ind C 422 (M⁺ + 1) N-i-154 NA N-i-153

H NMe2 1Me-5-Ind C 408 (M⁺ + 1)

TABLE-N-I-8 LCMS Exp. Syn SM1 SM2 NRzRy Y Zx AR method RTime MassN-i-121 NN2 N-i-77 CH₃I

Me NMe2 1Me-5-1HIdz C 423 (M⁺ + 1) N-i-122 NA N-i-121

H NMe2 1Me-5-1HIdz C 409 (M⁺ + 1) N-i-123 NN2 N-i-79 CH₃I

Me NMe2 2-Nap C 417 (M⁺ + 1) N-i-124 NA N-i-123

H NMe2 2-Nap C 403 (M⁺ + 1) N-i-125 NN2 N-i-83 CH₃I

Me NMe2 1Me-5-Ind C 420 (M⁺ + 1) N-i-126 NA N-i-125

H NMe2 1Me-5-Ind C 406 (M⁺ + 1) N-i-127 NN2 N-i-87 CH₃I

Me NMe2 1Me-5-1HIdz C 421 (M⁺ + 1) N-i-128 NA N-i-127

H NMe2 1Me-5-1HIdz C 407 (M⁺ + 1) N-i-129 NN2 N-i-91 CH₃I

Me NMe2 2-Nap C 431 (M⁺ + 1) N-i-130 NA N-i-129

H NMe2 2-Nap C 417 (M⁺ + 1) N-i-131 NN2 N-i-93 CH₃I

Me NMe2 1Me-5-Ind C 434 (M⁺ + 1) N-i-132 NA N-i-131

H NMe2 1Me-5-Ind C 420 (M⁺ + 1) N-i-133 NN2 N-i-97 CH₃I

Me NMe2 1Me-5-1HIdz C 435 (M⁺ + 1) N-i-134 NA N-i-133

H NMe2 1Me-5-1HIdz C 421 (M⁺ + 1) N-i-135 NN2 N-i-99 CH₃I

Me NMe2 2-Nap C 431 (M⁺ + 1) N-i-136 NA N-i-135

H NMe2 2-Nap C 417 (M⁺ + 1) N-i-137 NN2 N-i-103 CH₃I

Me NMe2 1Me-5-1HIdz C 435 (M⁺ + 1) N-i-138 NA N-i-137

H NMe2 1Me-5-1HIdz C 421 (M⁺ + 1)

Test Examples 1. Suppressing Action on PGE₂ Production fromIL-1β-stimulated MG-63 Cells (1) Method for Measurement

An action of suppressing PGE₂ production caused by interleukin (IL) 1βas an inflammatory stimulant was studied by the following method. Cellsof MG-63, which is a human osteosarcoma cell line (purchased fromDainippon Pharmaceutical), were suspended in EMEM medium (GIBCO)containing 10% fetal bovine serum (BioFluid), and then inoculated toeach well of 96-well culture plate at a density of 2×10⁴ cells/well andcultured overnight. The medium was changed to EMEM medium containing0.5% fetal bovine serum, and then a test compound was added to eachwell. Human interleukin-1β (ENDOGEN) was further added as aninflammatory stimulant at a final concentration of 1 ng/ml. The cellswere further cultured for 18 hours. Then, the culture supernatant wascollected, and the PGE₂ concentration in the culture supernatant wasmeasured by using EIA kit (CAYMAN). By using a well which was not addedwith the stimulant as a negative control and a well which was added onlywith the stimulant as a positive control, suppression ratio on PGE₂production was calculated from the produced amount of PGE₂ in the welladded with the test compound using the following equation.

PGE ₂ production suppression ratio=[1−(C−B)/(A−B)]×100  [Equation 1]

A: PGE₂ production amount of positive control

B: PGE₂ production amount of negative control

C: PGE₂ production amount in well added with test compound

Further, cytotoxicity of the compounds was studied by using the cellsafter the collection of the supernatant according to the methylene blueuptake method. Specifically, the cells remained after the collection ofthe supernatant were fixed with glutaraldehyde and stained with a 0.05%methylene blue solution, then methylene blue taken up by the cells wasextracted with 0.3 N hydrochloric acid, and absorbance of the extractwas measured at 670 nm. The absorbance of the well of the aforementionedpositive control was taken as 100%, and a test compound that gaveabsorbance in well of less than 80% was judged to be positive incytotoxicity.

(2) Measurement Results

The test compounds (Compound Nos. G-1 to G-121, H-1 to H-32, J-1 toJ-92, K-1 to K-40, L-1 to L-95, M-1 to M-32, N-1 to N-74, P-1 to P-50,Q-1 to Q-52, S-1 to S-73, T-1 to T-61, U-1 to U-18, V-1 to V-109, andW-1 to W-13) suppressed the PGE₂ production caused by IL-1β by 50% ormore at 1.0 μM. Moreover, all the test compounds did not exhibitcytotoxicity at that concentration.

The test compounds (Compound Nos. Ca-1 to Ca-203) suppressed the PGE₂production caused by IL-1β by 50% or more at 1.0 μM. None of the testcompounds exhibited cytotoxicity at that concentration.

The test compounds (Compound Nos. S-a-1 to S-a-24, S-b-1 to S-b-138, andS-c-1 to S-c-138) suppressed the PGE₂ production caused by IL-1 by 50%or more at 1.0 μM. None of the test compounds exhibited cytotoxicity atthat concentration.

Further, the test compounds (Compound Nos. N-a-1 to N-a-142, N-b-1 toN-b-182, N-c-1 to N-c-64, N-d-1 to N-d-74, N-e-1 to N-e-186 and N-g-1 toN-g-44) suppressed the PGE₂ production caused by IL-1β by 50% or more at1.0 μM. None of the test compounds exhibited cytotoxicity at thatconcentration.

Therefore, the novel substituted phenylalkanoic acid derivatives orsalts thereof according to the present invention are useful as agentsfor suppressing inflammatory prostaglandin production.

2. Suppressing Action on PGD₂ and LTB₄ Production from IgE-StimulatedRBL-2H3 Cells (1) Method for Measurement

Suppressing action on PGD₂ and LTB₄ production caused by IgE as anallergic stimulant was investigated by the following method. Cells ofRBL-2H3, which is a rat mastocytoma cell line (purchased from ATCC),were suspended in DEMEM medium (GIBCO) containing 10% fetal bovine serum(BioFluid), inoculated to each well of 48-well culture plate at adensity of 2×10⁴ cells/well and cultured overnight. Then, IgE antiserumdirected to dinitrophenylated BSA (hereinafter abbreviated as “DNP-BSA”)was further added to each well, and the cells were cultured for 30minutes. Then, the medium was changed to DEMEM medium containing 0.5%fetal bovine serum, a test compound was added to each well, and DNP-BSAwas further added at a final concentration of 100 ng/ml as a stimulant.Ten minutes after the stimulant was added, the culture supernatant wascollected, and the PGD₂ concentration and LTB₄ concentration in theculture supernatant were measured by using EIA kit (CAYMAN). By using awell which was not added with the stimulant as a negative control and awell which was added only with the stimulant as a positive control,suppressing ratios on mediator production were calculated from theproduction amounts of the mediators in the well added with the testcompound using the following equation 2.

PGD ₂ or LTB ₄ production suppressionratio=[1−(C−B)/(A−B)]×100  [Equation 2]

A: PGD₂ or LTB₄ production amount of positive control

B: PGD₂ or LTB₄ production amount of negative control

C: PGD₂ or LTB₄ production amount in well added with test compound

Cytotoxicity of the compounds was studied in the same manner as thosedescribed above, by using the cells after the collection of thesupernatant according to the methylene blue uptake method.

(2) Measurement Results

Representative compounds of the objective Compounds (I) described in thespecification suppressed the PGD₂ and LTB₄ production caused by IgEstimulation by 50% or more at 1.0 μM. Moreover, all the test compoundsdid not exhibit cytotoxicity at that concentration. Thus, the novelsubstituted phenylalkanoic acid derivatives or salts thereof accordingto the present invention exhibit suppressing action on the allergicprostaglandin and leukotriene production, and are useful as suppressingagents for the production thereof.

3. Suppressing Effect on Mouse Zymosan-Stimulated Footpad Edema Reaction(1) Method for Measurement

A suppressing effect on footpad edema caused by zymosan as aninflammatory stimulant was studied by the following method. Groups ofICR female mice (6- to 7-week old) each consisting of eight mice wereused for the test. A test compound was suspended or dissolved inpurified water containing 0.5% methylcellulose and orally administeredto the test animals at 0.1 to 500 mg/10 ml/kg. To the control group,purified water containing 0.5% methylcellulose was administered in asimilar manner, which was not added with a test compound. One hour afterthe administration of the test compound, 0.02 ml of a suspension ofzymosan suspended in physiological saline (Otsuka Pharmaceutical) at 1mg/ml was subcutaneously administered to right hind leg footpad of eachmouse. One and two hours after the administration of the zymosansuspension, volume of the right hind leg footpad was measured by usingan apparatus for measuring a volume of mouse hind leg footpad edema(Unicom). A difference of the volume of footpad measured above and thefootpad volume before the administration of the test compound measuredbeforehand was regarded as a volume of the edema.

For the volume of the edema at 1 hour or 2 hours after the zymosanadministration, a graph was prepared by indicating time in abscissa andthe edema volume in ordinate, and an edema volume AUC (area under thecurve) was obtained up to 2 hours by calculation using the followingequation.

Edema volume AUC(μl·hour)=½×1×A+1×(A+B)/2  [Equation 3]

A: Edema volume 1 hour after zymosan administration

B: Edema volume 2 hour after zymosan administration

A suppression ratio on edema of test compound was obtained bycalculation using the following equation.

Edema suppression ratio(%)=[1−B/A]×100  [Equation 4]

A: Edema volume AUC of positive control

B: Edema volume AUC of test compound administered group

(2) Measurement Results

Representative compounds of the objective Compounds (I) described in thespecification more effectively suppressed footpad edema caused bysubcutaneous administration of zymosan compared with the positivecontrol group by oral administration at 0.1 to 500 mg/kg.

Therefore, the novel substituted phenylalkanoic acid derivatives orsalts thereof according to the present invention exhibit a suppressingaction on footpad edema caused by zymosan as an inflammatory stimulant,and thus they are useful as agents for prophylactic and/or therapeuticdrugs for inflammatory diseases.

4. Suppressing Effect on Mouse IgE-Stimulated Footpad Edema Reaction (1)Method for Measurement

Suppression on footpad edema caused by IgE antibody as an allergicstimulant was studied by the following method. Groups of C⁵⁷BL/6 malemice (9- to 11-week old) each consisting of five mice were used for thetest. Anti-DNP-BSA IgE serum was subcutaneously administered in a volumeof 20 μl to right hind leg footpad of each mouse one day before thetest. A test compound was suspended or dissolved in purified watercontaining 0.5% methylcellulose and orally administered to the testanimals at 0.1 to 500 mg/10 ml/kg. To the control group, purified watercontaining 0.5% methylcellulose was administered in a similar manner,which was not added with any test compound. Two hours after theadministration of the test compound, 0.2 ml of a solution of DNP-BSAdissolved in physiological saline (Otsuka Pharmaceutical) at 2.5 μg/mlwas intravenously administered. The thickness of right hind leg footpadwas measured by using a digital thickness gauge (MITSUTOYO) 10, 15, 20,and 30 minutes after the administration of DNP-BSA. A difference of thethickness of footpad measured above and the thickness before theadministration of the test compound measured beforehand was regarded asa thickness of edema.

For the thickness of the edema at 10, 15, 20 and 30 minutes after theDNP-BSA administration, a graph was prepared indicating time in abscissaand the edema thickness in ordinate, and edema thickness AUC up to 2hours was obtained by calculation according to the following equation.

Edema thicknessAUC(mm·minute)=½×10×A+5×(A+B)/2+5×(B+C)/2+10×(C+D)/2  [Equation 5]

A: Edema thickness 10 minutes after DNP-BSA administration

B: Edema thickness 15 minutes after DNP-BSA administration

C: Edema thickness 20 minutes after DNP-BSA administration

D: Edema thickness 30 minutes after DNP-BSA administration

A suppressing ratio on edema of a test compound was obtained bycalculation in accordance with the following equation.

Edema suppression ratio(%)=[1−B/A]×100  [Equation 6]

A: Edema thickness AUC of positive control

B: Edema thickness AUC of test compound administered group

(2) Measurement Results

Representative compounds of the objective Compounds (I) described in thespecification suppressed the footpad edema caused by IgE stimulation,i.e., footpad edema observed when DNP-BSA was administered to the micesensitized with the anti-DNP-BSA IgE serum, compared with the positivecontrol group by oral administration of 0.1 to 500 mg/kg.

Therefore, the novel substituted phenylalkanoic acid derivatives orsalts thereof according to the present invention exhibit suppressingaction on footpad edema caused by IgE antibody, which is an allergicstimulant, and thus they are useful as prophylactic and/or therapeuticdrugs for allergic diseases.

5. Suppressing Effect on Mouse Acetic Acid Writhing Reaction (1) Methodfor Measurement

A suppressing effect on acetic acid writhing reaction, which is an acutepain model, was studied by the following method. Groups of ICR femalemice (6-week old) each consisting of eight mice were used for the test.A test compound was suspended or dissolved in purified water containing0.5% methylcellulose and orally administered to the test animals at 0.1to 500 mg/10 ml/kg. To the control group, purified water containing 0.5%methylcellulose was administered in a similar manner, which was notadded with any test compound. One hour after the administration of thetest compound, 0.9% aqueous acetic acid was intraperitoneallyadministered to the mice in a volume of 5 ml/kg, and number of writhingreactions during 15 minutes immediately after the administration ofacetic acid was counted. Suppression ratio relative to the control groupwas obtained by calculation according to the following equation.

Writhing suppression ratio(%)=[1−B/A]×100  [Equation 7]

A: Writhing number of positive control group

B: Writhing number of test compound administered group

(2) Measurement Results

The representative compounds of the objective Compounds (I) described inthe specification suppressed writhing caused by administration ofaqueous acetic acid compared with the positive control group at oraladministration of 0.1 to 500 mg/kg.

It has been elucidated that a writhing reaction caused byintraperitoneal administration of acetic acid is caused due toproduction of prostaglandin [Matsumoto et al., European Journal ofPharmacology (Eur. J. Pharmacol), 1998, vol. 352, p. 47; Ueno et al.,Biochemical Pharmacology (Biochem. Pharmacol), 2001, vol. 15, p. 157].

Therefore, the novel substituted phenylalkanoic acid derivatives orsalts thereof according to the present invention are useful asprophylactic and/or therapeutic agents for acute pain caused byprostaglandins.

6. Prophylactic and Therapeutic Effects for Rat Adjuvant Arthritis (1)Method for Measurement

A suppressing effect on footpad edema observed in rat adjuvantarthritis, which is a disease model of rheumatoid arthritis as being oneof autoimmune diseases and also a chronic inflammatory disease, wasstudied by the following method. Groups of Lewis female rats (8-weekold) each consisting of six mice were used for the test. The testanimals were immunized by subcutaneously administering, to right hindleg footpads, 50 μl of liquid paraffin containing 10 mg/ml of M.tuberclulosis H37 RA (DIFCO) as an adjuvant. A test compound wassuspended or dissolved in purified water containing 0.5% methylcelluloseand orally administered to the test animals at 0.1 to 500 mg/5 ml/kg.The test compound was administered twice a day for 14 days, from the12th day after the immunization. To the control group, purified watercontaining 0.5% methylcellulose was administered in a similar manner,which was not added with any test compound. Every 2 or 3 days after theadministration of adjuvant, volume of left hind leg footpad, which wasnot administered with the adjuvant, was measured by using an apparatusfor measuring a volume of edema of a rat hind leg footpad (Unicom). Asuppression ratio on edema was obtained by calculation using thefollowing equation.

Edema suppression ratio(%)={1−[(D−C)/C]/[(B−A)/A]}×100  [Equation 8]

A: Left hind leg footpad volume of positive control immediately beforeadministration of adjuvant

B: Left hind leg footpad volume of positive control on each measurementday

C: Left hind leg footpad volume of test compound administered groupimmediately before administration of adjuvant

D: Left hind leg footpad volume of test compound administered group oneach measurement day

(2) Measurement Results

The representative compounds of the objective Compound (I) described inthe specification suppressed footpad edema in adjuvant arthritiscompared with the positive control group.

Therefore, the novel substituted phenylalkanoic acid derivatives orsalts thereof according to the present invention are useful as agentsfor prophylactic and/or therapeutic drugs for rheumatoid arthritis andautoimmune diseases.

7. Effect on Rat Pulmonary Fibrosis (1) Method for Measurement

A suppressing effect on pulmonary fibrosing in a bleomycin-induced ratpulmonary fibrosis model, which is a pathological model of pulmonaryfibrosis, was studied by the following method. Groups of BN female rats(7-week old) each consisting of seven rats were used for the test. Thetest animals were anesthetized with ketamine and xylazine, and thetracheae were exposed. Then, a 125 μg/0.1 ml solution of bleomycin(Nippon Kayaku) dissolved in physiological saline (OhtsukaPharmaceutical Factory) was injected into the tracheae by using asyringe. The negative control group was administered with 0.1 ml ofsaline into the tracheae.

Each test compound was suspended or dissolved in purified watercontaining 0.5% methylcellulose, and orally administered to the testanimals at doses of 10, 30, 100 and 300 mg/5 ml/kg. The administrationof the test compounds was started from the day of the bleomycinadministration and performed once or twice a day for 21 days. Thepositive control group was administered with purified water containing0.5% methylcellulose not added with any test compound in a similarmanner. On the 21st day after the administration of bleomycin, the ratswere sacrificed, and lungs were fixed with neutral buffered formalin toprepare histopathological samples. Staining of the histopathologicalsamples was performed by the Azan method.

The histopathological samples of lungs were examined, and degree offibrosing was represented with the following scores on the basis offormation of granulation tissues and proliferation of collagen fibers asindicators, i.e., −: no abnormality, ±: extremely mild change, +: mildchange, ++: moderate change, and +++: significant change.

(2) Measurement Results

The fibrosing score of the negative control group was minus (−), and nopulmonary fibrosing was observed. The median of the fibrosing score ofthe positive control group was from ++ to +++, and pulmonary fibrosingwas observed. The medians of the fibrosing score of the groups of ratsadministered with the test compounds (Compound Nos. G-2, G-4 and V-40)were from ± to +, and thus the fibrosing was milder compared with thepositive control group. The median of the fibrosing score of the groupadministered with the other test compounds (Compound Nos. G118 and V-59)was from ± to +, and thus pulmonary fibrosing was milder that thatobserved in the positive control group. Accordingly, the compounds ofthe present invention are useful as a prophylactic and/or therapeuticagent for pulmonary fibrosis, and type 4 PLA₂ inhibitor compounds areuseful as a prophylactic and/or therapeutic agent (including aprogression-preventing agent) for pulmonary fibrosis.

Further, known cPLA₂ inhibitory compounds, arachidonyl trifluoromethylketone, 4-(1-benzhydryl-6-chloro-1H-indol-3-ylmethyl)-3-methoxybenzoicacid,N-{1-[2-(2,4-difluorobenzoyl)benzoyl]-4-tritylsulfanylpyrrolidin-2-ylmethyl}-4-(2,4-dioxothiazolidin-5-ylidenemethyl)benzoicacid amide and4-{4-[2-(2-[bis(4-chlorophenyl)methoxy]ethylsulfonyl)ethoxy]phenyl}-1,1,1-trifluoro-2-butanone,are intraperitoneally or orally administered in a similar manner.Fibrosing is mild also in the groups administered with these known type4 PLA₂ inhibitory compounds.

INDUSTRIAL APPLICABILITY

The compounds of the present invention have superior suppressing actionon prostaglandin production and leukotriene production, and they areuseful as active ingredients of medicaments for prophylactic and/ortherapeutic treatment of various inflammatory diseases, autoimmunediseases, allergic diseases, pain, fibrosis and the like caused by theselipid mediators.

1. A compound represented by the following formula (III):

in the formula, C²′, C³′, C⁴′, C⁵′, and C⁶′ in the aromatic ring (E′)represents a ring-constituting carbon atom, any one of these atoms towhich Rs′ and AR′ does not bind may be replaced with V′, and AR′ has thesame meaning as that of AR, provided that when AR contains hydroxylgroup, the hydroxyl group may be protected with Rp¹, and when ARcontains amino group, the amino group may be protected with Rp².
 2. Thecompound according to claim 1, wherein, in the formula (III), AR′ bindsto the atom of C²′ or C³′ in the aromatic ring (E′).
 3. The compoundaccording to claim 1, wherein, in the formula (III), AR′ isnaphthalen-2-yl group, naphthale-1-yl group, benzofuran-5-yl group,benzofuran-4-yl group, benzofuran-2-yl group, benzo[b]thiophen-5-ylgroup, benzo[b]thiophen-4-yl group, benzo[b]thiophen-2-yl group, indol-5yl group, indol-4-yl group, indol-6-yl group, benzothiazol-6-yl group,benzothiazol-7-yl group, benzothiazol-5-yl group, benzothiazol-4-ylgroup, dihydro-3H-benzothiazol-6-yl group, dihydro-3H-benzothiazol-7-ylgroup, dihydro-3H-benzothiazol-5-yl group, dihydro-3H-benzothiazol-4-ylgroup, quinolin-6-yl group, quinolin-3-yl group, quinolin-5-yl group,quinolin-7-yl group, dihydro-3H-quinolin-6-yl group,dihydro-3H-quinolin-5-yl group, benzo[d]isothiazol-5-yl group,benzo[d]isothiazol-4-yl group, benzo[d]isothiazol-6-yl group,benzo[d]isothiazol-7-yl group, 1H-indazol-5-yl group, 1H-indazol-4-ylgroup, 1H-indazol-6-yl group, benzo[c]isothiazol-5-yl group,benzo[c]isothiazol-4-yl group, benzo[c]isothiazol-6-yl group,benzo[c]isothiazol-7-yl group, 2H-indazol-5-yl group, 2H-indazol-4-ylgroup, 2H-indazol-6-yl group, imidazo[1,2-a]pyridin-6-yl group,imidazo[1,2-a]pyridin-7-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1H-pyrrolo[2,3-b]pyridin-4-yl group, isoquinolin-6-yl group,isoquinolin-3-yl group, isoquinolin-5-yl group, isoqinolin-7-yl group,dihydro-2H-isoquinolin-6-yl group, dihydro-2H-isoquinolin-5-yl group,cinnolin-6-yl group, cinnolin-5yl group, quinazolin-6-yl group,quinazolin-7-yl group, quinazolin-5-yl group, quinoxalin-2-yl group,quinoxalin-6-yl group, quinoxalin-5-yl group, 1H-benzimidazol-5-ylgroup, 1H-benzimidazol-4-yl group, benzoxazol-5-yl group,benzoxazol-6-yl group, benzoxazol-4-yl group, benzoxazol-7-yl group,1H-pyrrolo[3,2-b]pyridin-5-yl group, 1H-pyrrolo[3,2-b]pyridin-6-ylgroup, benzo[1,2,5]thiadiazol-5-yl group, benzo[1,2,5thiadiazol-4-ylgroup, 1H-benzotriazol-5-yl group, 1H-benzotriazol-4-yl group,1,3-dihydropyrrolo[2,3b]pyridin-5-yl group,1,3-dihydropyrrolo[2,3b]pyridin-4-yl group, 1,3-dihydrobenzimidazol-5-ylgroup, 1,3-dihydrobenzimidazol-4-yl group, dihydro-3H-benzoxazol-6-ylgroup, dihydro-3H-benzoxazol-7-yl group, dihydro-3H-benzoxazol-5-ylgroup, dihydro-3H-benzoxazol-4-yl group, phthalazin-6-yl group,phthalazin-5-yl group, [1,8]naphthalidin-3-yl group,[1,8]naphthalidin-4-yl group, [1,5]naphthalidin-3-yl group,[1,5]naphthalidin-4-yl group, 1H-pyrrolo[3,2-c]pyridin-6-yl group,1H-pyrrolo[3,2-c]pyridin-4-yl group, 1H-pyrrolo[2,3-c]pyridin-5-ylgroup, 1H-pyrrolo[2,3-c]pyridin-4-yl group,1H-pyrazolo[4,3-b]pyridin-5-yl group, 1H-pyrazolo[4,3-b]pyridin-6-ylgroup, 1H-pyrazolo[4,3-c]pyridin-6-yl group,1H-pyrazolo[4,3-c]pyridin-4-yl group, 1H-pyrazolo[3,4-c]pyridin-5-ylgroup, 1H-pyrazolo[3,4-c]pyridin-4-yl group,1H-pyrazolo[3,4-b]pyridin-5-yl group, 1H-pyrazolo[3,4-b]pyridin-4-ylgroup, [1,2,4]triazolo[4,3-a]pyridin-6-yl group,[1,2,4]triazolo[4,3-a]pyridin-7-yl group, thieno[3,2-c]pyridin-2ylgroup, thieno[3,2-c]pyridin-3-yl group, thieno[3,2-c]pyridin-6-yl group,thieno[3,2-b]pyridin-2-yl group, thieno[3,2-b]pyridin-3-yl group,thieno[3,2-b]pyridin-5-yl group, thieno[3,2-b]pyridin-6-yl group,1H-thieno[3,2-c]pyrazol-5-yl group, 1H-thieno[3,2-c]pyrazol-4-yl group,benzo[d]isoxazol-5-yl group, benzo[d]isoxazol-4-yl group,benzo[d]isoxazol-6-yl group, benzo[d]isoxazol-7-yl group,benzo[c]isoxazol-5-yl group, benzo[c]isoxazol-4-yl group,benzo[c]isoxazol-6-yl group, benzo[c]isoxazol-7-yl group, indolizin-7-ylgroup, indolizin-6-yl group, indolizine-8-yl group,1,3-dihydroindol-5-yl group, 1,3-dihydroindol-4-yl group,1,3-dihydroindol-6-yl group, 1H-pyrazolo[3,4-d]thiazol-5-yl group,2H-isoindol-5-yl group, 2H-isoindol-4-yl group,[1,2,4]triazolo[1,5-a]pyrimidin-6-yl group,1H-pyrazolo[3,4-b]pyrazin-5-yl group, 1H-imidazo[4,5-b]pyrazin-5ylgroup, 7H-purin-2-yl group, 4H-chromen-6-yl group, or 4H-chromen-5-ylgroup (the aforementioned groups may be substituted with one of Xa ortwo or more of the same or different Xa, when AR′ contains hydroxylgroup, the hydroxyl group may be protected with Rp¹, and when AR′contains amino group, the amino group may be protected with Rp²).
 4. Thecompound according to claim 1, wherein, in the formula (III), AR′ bindsto C³′ in the aromatic rig (E′), Rs′ binds to C⁴′ in the aromatic ring(E′), C⁵′ is carbon atom substituted with —N(Rn¹)(Rn²) (provided thatone of Rn¹ and Rn² is a substituent other than hydrogen atom), C²′ andC⁶′ are unsubstituted ring-constituting carbon atoms, and Rs′ is —O-Rx′.5. The compound according to claim 1, wherein, in the formula (III), C³′is carbon atom to which AR′ binds, C⁴′ is carbon atom to which Rs′binds, C³′ is carbon atom substituted with Zx′, C²′ and C⁶′ aresubstituted ring-constituting carbon atoms, Zx′ is N-methylamino group,N-ethylamino group, N-propylamino group, N-isopropylamino group,N,N-dimethylamino group, N,N-diethylamino group, formylamino group,acetylamino group, carbamoylamino group, mesylamino group, orN,N-dimethylsulfamoylamino group, provided that when Zx′ contains aminogroup, the amino group may be protected with Rp², Rs′ is —O—Rx′, Rx′ isbutyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group,cyclohexyl group, cycloheptyl group, cyclopentylmethyl group,cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group,2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group,2chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group,indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group,4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group,4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group,4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group,4-chloroindan-2-yl group, 5-chloroindan-2-yl group,4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group,4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group,4,7-dimethoxyindan-2 yl group, 5,6-dimethoxyindan-2-yl group,1-phenylethyl group, 1-(2-fluorophenyl)ethyl group,1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group,1-(2-chlorophenyl)ethyl group, 1-(3chlorophenyl)ethyl group,1-(4chlorophenyl)ethyl group, 2-methylphenylmethyl group,3-methylphenylmethyl group, 4-methylphenylmethyl group,2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group,2-fluorophenylmethyl group, 3-fluorophenylmethyl group,4-fluorophenylmethyl group, 2-chlorophenylmethyl group,3-chlorophenylmethyl group, 4-chlorophenylmethyl group,2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group,2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group,2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group,2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group,3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group,3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group,3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethylgroup, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group,2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group,2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group,2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group,2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group,2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group,2-[2-(trifluoromethyl)phenyl]ethyl group,2-[3-(trifluoromethyl)phenyl]ethyl group,2-[4-(trifluoromethyl)phenyl]ethyl group,2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group,2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group,2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group,2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethylgroup, and AR′ is naphthalen-2-yl group, 6-hydroxynaphthalen-2-yl group,6-methoxynaphthalen-2-yl group, 6-(2-hydroxyethyloxy)naphthalen-2-ylgroup, 6-aminonaphthalen-2-yl group, 6-(N-methylamino)naphthalen-2-ylgroup, 6-(N,N-dimethylamino)naphthalen-2-yl group,6-(2-hydroxyethylamino)naphthalen-2-yl group, benzo[b]furan-5-yl group,2-methylbenzo[b]furan-5-yl group, 3-methylbenzo[b]furan-5-yl group,2,3-dimethylbenzo[b]furan-5-yl group, benzo[b]thiophen-5-yl group,2-methylbenzo[b]thiophen-5-yl group, 3-methylbenzo[b]thiophen-5-ylgroup, 2,3-dimethylbenzo[b]thiophen-5-yl group, 1H-indol-5-yl group,2-methyl-1H-indol-5-yl group, 3-methyl-1H-indol-5-yl group,2,3-dimethyl-1H-indol-5-yl group, 1-methyl-1H-indol-5-yl group,1,2-dimethyl-1H-indol-5-yl group, 1,3-dimethyl-1H-indol-5-yl group,1,2,3-trimethyl-1H-indol-5-yl group, 1-ethyl-1H-indol-5-yl group,1-ethyl-2-methyl-1H-indol-5-yl group, 1-ethyl-3-methyl-1H-indol-5-ylgroup, 1-ethyl-2,3-dimethyl-1H-indol-5-yl group, 1-propyl-1H-indol-5-ylgroup, 2-methyl-1-propyl-1H-indol-5-yl group,3-methyl-1-propyl-1H-indol-5-yl group,2,3-dimethyl-1-propyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-1H-indol-5-yl group,1-(2-hydroxyethyl)-2-methyl-1H-indol-5-yl group,1-(2-hydroxyethyl)-3-methyl-1H-indol-5-yl group,2,3-dimethyl-1-(2-hydroxyethyl)-1H-indol-5-yl group, benzothiazol-6-ylgroup, 2-methylbenzothiazol-6-yl group, 2-methoxybenzothiazol-6-ylgroup, 2-aminobenzothiazol-6-yl group,2-oxo-2,3-dihydrobenzothiazol-6-yl group,2-oxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-2,3-dihydrobenzothiazol-6-yl group,2-thioxo-3-methyl-2,3-dihydrobenzothiazol-6-yl group, quinolin-3-ylgroup, quinolin-6-yl group, 2-oxo-1,2-dihydroquinolin-6-yl group,benzo[d]isothiazol-5-yl group, 1H-indazol-5-yl group,1-methyl-1H-indazol-5-yl group, 1-ethyl-1H-indazol-5-yl group,1-propyl-1H-indazol-5-yl group, 1-(2-hydroxyethyl)-1H-indazol-5-ylgroup, -yl group, 1-ethyl-3-hydroxy-1H-indazol-5-yl group,imidazo[1,2-a]pyridin-6-yl group, 1H-pyrrolo[2,3-b]pyridin-5-yl group,1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-propyl-1H-pyrrolo[2,3-b]pyridin-5-yl group,1-(2-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl group, isoquinolin-6-ylgroup, 1-oxo-1,2-dihydroisoquinolin-6-yl group, cinnolin-6-yl group, orbenzoxazol-5-yl group, provided that when AR′ contains hydroxyl group,the hydroxyl group may be protected with Rp¹, and when AR′ containsamino group, the amino group may be protected with Rp².
 6. The compoundaccording to claim 1, wherein, in the formula (III), AR′ binds to C³′ inthe aromatic ring (E′), Rs′ binds to C⁴′ in the aromatic ring (E′), C⁵′is carbon atom substituted with nitro group, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms, and Rs′ is —O-Rx′.
 7. Thecompound according to claim 3, wherein, in the formula (III), AR′ bindsto C³′ in the aromatic ring (E′), Rs′ binds to C⁴′ in the aromatic ring(E′), C⁵′ is carbon atom substituted with nitro group, C²′ and C⁶′ areunsubstituted ring-constituting carbon atoms, and R⁵ ′ is —O-Rx′.